We are searching data for your request:
Upon completion, a link will appear to access the found materials.
The synaptic clefts are really small, but the neurones which they are between do not touch even against forces like gravity.
What really prevents them from coming into direct contact at the synapse, and also what would happen if they did come into contact?
Neural Control and Coordination Important Extra Questions Very Short Answer Type
What are the major divisions of the forebrain?
Cerebrum, Thalamus, Hypothalamus.
Which parts of the central nervous system constitute the grey matter?
Areas that contain cell bodies of the neurons.
Name the major lobes of the cerebral hemisphere?
Frontal, parietal, temporal and occipital.
What is the function of cerebral spinal fluid?
It maintains a constant pressure inside the cranium.
What is the junction between two neurons known as?
What is the polarized state of the nerve membrane?
It is the state of the nerve membrane when its inner side is electronegative to its outer side.
Give two examples of unconditioned reflexes.
(i) Salivation on tasting food.
(ii) Constriction of the pupil on the illumination of the eye.
Name the types of cells present in the retina.
Rods, cones, bipolar neurons, ganglion cells, supporting cells.
Where is iodopsin present in the eye?
In the cone cells of the retina
Where are taste buds located?
In the mucous membrane over the papillae on the tongue.
Name the main parts of the human brain.
Cerebrum, cerebellum, medulla, thalamus, and hypothalamus.
How many cranial nerves and spinal nerves do we possess?
12 pairs of cranial nerves and 31 pairs of spinal nerves.
Which part of the brain controls posture and equilibrium?
What is a polarised membrane?
It is electrically positive outside and negative inside.
Compare rods and cones.
Rods work in dim light and dark. Cones work in bright light.
What is the blind spot?
The point of the retina from where the optic nerve starts and receptor cells are absent.
Neural Control and Coordination Important Extra Questions Short Answer Type
What are receptors?
Receptors are peripheral nerve endings in the skin or special sense organs. They collect information from the external or internal environment of the body transform them into electrical potential changes, which then pass along the afferent neurons to CNS.
Why does vitamin A deficiency produce night blindness?
Vitamin ‘A’ is the constituent of rhodopsin, a pigment present in the photoreceptor cells of the eye. Rhodopsin breaks up into opsin and rode to visualize things in bright and dim light. There is constant consumption of vitamin A in rod cells. Deficiency of vitamin A causes impairment of synthesis of rhodopsin leading to night blindness, i.e., inability to see in the dark.
Why does the nerve impulse flow more rapidly in myelinated nerve fibers than in the non-myelinated fibers?
Due to the following reasons nerve impulse flows more rapidly in myelinated nerve fibers:
- Myelin sheath provides insulation to the nerve fibers from electrical disturbances between the neighboring fibers.
- Myelin sheath is impermeable to free ions present in the extracellular fluid. So, it prevents the exchange of ions between the extracellular fluid and the interior of the myelinated axon.
- The myelin sheath is absent at the Nodes of Ranvier, so, action potential jumps from one Node of Ranvier to the next. Thus, the nerve impulse flows in the form of leaps or jumps. This is known as the saltatory conduction of impulse.
- It is more rapid than the smooth flow of impulse.
What is a synapse?
It is the junction between axon terminals of a neuron and dendrites or the cell body of another neuron. There is a narrow fluid-filled space, called Synaptic Cleft separating axon terminals and dendrites at the synaptic junction. So, the two-neurons forming synapse does not form actual continuity between the neurons.
Structure of Synapse
Draw a labeled diagram of a section of the retina to illustrate its structure.
Diagrammatic representation of the sectional view of the retina.
What functions does the hypothalamus serve in coordinating the various activities of the body?
- It contains nerve centers for temperature regulation, hunger, thirst, and emotional reactions.
- It secretes neurohormones, which control the secretion of anterior pituitary hormones.
- It synthesizes the posterior pituitary hormones and controls their release into the blood.
What is a nerve fiber? How is it classified according to myelin sheath?
A nerve fiber is a long axon or dendrite of a neuron. According to the presence and absence of myelin sheath around the fibers.
- Myelinated nerve fiber (i.e., presence of myelin sheath) and
- Non-myelinated nerve fiber (i.e., absence of myelin sheath).
Explain Motor-end plate.
A Motor-end plate is a specialized structure formed by the muscle fiber at the point where the axon terminal is applied to it. The axon of the motor neuron is divided into branches near the muscle fibers. Each branch loses its myelin sheath near its termination and ends in an expanded foot-like form which is supplied closely to a muscle fiber.
There is no actual continuity between the neuron and muscle fiber. The membranes of the two are separated from each other by a narrow cleft-like fluid-filled space.
What are the biological functions of Dorsal and Ventral spinal nerve roots fibers?
Dorsal spinal nerve root fibers bring impulses from the peripheral tissues, giving rise to sensations like touch, temperature, and pain, or to involuntary spontaneous activities called Reflexes.
Ventral spinal nerve root fibers: Some of the root fibers go to skeletal muscle fibers directly to stimulate or inhibit their activities many others go to autonomic ganglia and end in them.
Our rods and cones evenly distributed over the entire surface of the retina? Why or not? At which point on the retina is a point-to-point image formed?
The retina is composed of several layers of cells. First, there are the photoreceptor cells, the rods, and cones, partially embedded in the microvilli of pigmented epithelium cells of the choroids. The rod cells are present on the periphery of the retina in the human eye. The total number of rod cells has been estimated to be between 110 – 125 million. They contain a visual pigment called Rhodopsin.
The cone cells are shorter, thicker, and conical in shape. Cone cells are responsible for the perception of different colors. The total number of cone cells is 6.36 – 6.8 million. Cones are abundant on the rear wall and fovea centralis of the retina.
The point-to-point image is formed on the blind spot. From it, the optic nerve and blood vessels exit the retina and join the diencephalon of the brain.
Blindspot in the eye is devoid of the ability of vision. Why is it so?
It is devoid of rods and cone cells. It is unstable to light rays.
If a strong odor is smelled continuously for some time, the sensation of that weakens. Justify.
When a person continuously inhales the fumes in the air of a strong-smelling substance the sense of smell progressively and rapidly declines and finally disappears. This is because the olfactory cells get fatigued rapidly due to overstimulation. This is called olfactory adaptation, which develops from various changes in the olfactory epithelium and olfactory centers of the brain.
Which part of the nervous system participates in the maintenance of balance and co-ordinate body movements?
The cerebellum process all the data and co-ordinates muscle movement in conjunction with the cortex and sends signals to the muscles to adjust.
What is a reflex action? What units of the nervous systems are involved with a typical vertebrate reflex arc?
It is a spontaneous, automatic, mechanical, nerve-mediated response evoked at the unconscious level by the stimulation of any specific receptor without exercising the will of an organism.
There, are more than 200 reflexes “wired” into our nervous system all following the sequence from stimulus to reflex along the specific neural pathway that makes up the reflex arc. The simplest reflex arc involves some specific receptor, afferent sensory neuron towards an aggregation of nervous tissue which may be ganglion or the spinal cord.
Which nerve tract connects the right and left hemispheres of the cerebrum? Into what four lobes in each hemisphere divided?
A longitudinal fissure splits the brain into two halves, the left, and right cerebral hemispheres. Other grooves divide the surface of each cerebral hemisphere into four lobes. The frontal lobe, temporal lobe at the front, parietal lobe, and occipital lobe at the back.
What is the primary function of neuroglia cells? What special structure is produced by Schwann cells?
The neuroglia cells perform many house-keeping functions, provide nutritional support to the neurons and consume waste products. They also insulate, separating each neuron from the others.
Schwann cells, a type of neuroglial, wrap around the axon with concentric layers of the insulating plasma membrane.
How does a wave of depolarization spread along with a nerve fiber?
Nerve cells have polarized membranes, having an electrical potential difference across the membrane. The trigger zone for a particular neuron is the place on the membrane where voltage-gated channels are clustered most densely. When stimulated opening of voltage-gated Na + ion channel brings Na + ions into the cell, a temporary, very localized, but rapid inflow of Na + ions into the cells occurs, wiping out the local electrical potential difference in the immediate vicinity. This is called depolarization.
When the site of stimulation has less charge difference than the membrane surface surrounding it, this potential difference establishes a small, localized current in the immediate vicinity, which influences the nearby Na + channels to open and depolarizing these cells.
The depolarization thus spreads, producing a local current, which induces passive Na + channels to open and so to depolarize the near % site. In this way, initial depolarization passes outward over the membrane and spreads out in all directions along with the nerve fiber, from dendron to axon.
What is a synapse? How does the nerve cell across the synapse?
A nerve signal travels from neuron to neuron all around the body. These associations are called Synapse.
There are mainly two types of synapses:
- Electrical and
- Chemical depending upon the nature of the transfer of information across the synapse.
In electrical synapses, cells are separated by a gap, the synaptic cleft, of only 0.2 mm. So that an action potential arriving at the presynaptic side of the cleft can sufficiently depolarize the postsynaptic membrane to directly trigger its action potential.
Chemical synapses are the common type of synapse consists of a bulbous expansion of a nerve terminal called a synaptic knob. The cytoplasm of the synaptic knob contains numerous tiny round sacs synaptic vesicles. Each vesicle contains a neurotransmitter substance responsible for the transmission of nerve impulses across the synapse.
What is the action potential of a neuron? Do all neurons possess the same action potential?
Depolarisation is caused by rapid change in membrane permeability and a corresponding shift in the balance of ions. If the shift of ions and consequent shift in electrical charges is sufficient, it will trigger a wave of transient membrane depolarisation known as nerve impulse or Action potential. Different neurons possess different densities of Na + ion channels, different neurons exhibit different action potentials. However, for anyone neuron, the action potential is always the same.
Why is the mode of conduction of electrical impulse along the myelinated neuron is advantageous to a non-myelinated neuron? What is this type of conduction called?
The myelinated nerve fibers carry impulses nearly 20 times faster than the non-myelinated nerve fibers. These avoid the dissipation of impulses into adjacent fibers. The myelin sheath serves as a highly insulating layer that prevents the flow of ions between the fluid external to the myelin sheath and within the axon.
In non-myelinated fiber, ionic charges and depolarization are repeated over the membrane along the length of the fiber and action potential flow over the entire length of the fiber. But in myelinated fibers, ionic changes and depolarization are repeated only at the nodes. Thus the impulse is more rapid in myelinated fibers and requires less energy. This jumping of depolarization from node to node is called saltatory conduction of nerve impulse.
(a) Make a clearly labeled diagram of the inner ear of a human being.
Diagrams showing the inner ear
(b) Describe how each of the following is achieved in us
Neural Control and Coordination Important Extra Questions Long Answer Type
(a) Describe the reflex arc with a diagram.
The neurons forming the pathway taken by the nerve impulses in the reflex action form the Reflex Arc.
The reflex arc consists of
- An afferent neuron or sensory neurons from receptor to CN system,
- The efferent neuron of motor neurons from CN system to specific muscle fibers or gland cells,
- a number of connectors or intermediate neurons conducting impulses form the afferent to the efferent neurons.
When a specific stimulus is applied to a specific group of receptors, it stimulates the receptor to initiate a nerve impulse along the afferent neurons. This impulse travels along with the afferent connector and efferent neurons to reach an effector-muscle or gland for that reflex. Thus the flow of impulse can only be in a single direction in a reflex arc, i.e.,
Stimulus → receptor → afferent neuron → CN system efferent neuron ← (connector neuron)
(b) Distinguish between conditioned reflex and unconditioned reflex.
Differences between conditioned reflex and unconditioned reflex:
|Conditioned Reflex||Unconditioned Reflex|
|It is a reflex, acquired after birth by applying an indifferent stimulus before or along with the stimulus for an inborn reflex.||It is a reflex, which can be evoked even immediately after birth and needs no previous encounter with the stimulus exciting it.|
(a) Give an account of spinal nerves in man.
There are 31 pairs of a spinal nerve in man. From each segment of the spinal cord, there are two spinal nerves. Each spinal nerve is a mixed nerve, containing both sensory and motor nerve fibers. It runs between the spinal cord and peripheral tissue. The two roots, i.e., motor or ventral and sensory or dorsal connect the spinal nerve to the spinal cord.
The DORSAL ROOT carries sensory or afferent fiber and has a dorsal root ganglion at its middle. The VENTRAL ROOT contains a motor or efferent nerve fibers. The dorsal root fibers bring impulses from the peripheral tissue and give rise to sensations like touch, temperature, and pain.
The ventral nerve root fibers pass impulses to muscles and glands in the peripheral tissues. The spinal nerve has been named according to its relation with the vertebral column.
- Eight pairs of cervical
- 12 pairs of thoracic
- 5 pairs of lumber,
- 5 pairs of sacral and
- a pair of coccygeal or caudal.
(b) What biological functions are served by the skeletal system?
- The skeletal system forms the rigid structural framework of the body and supports the weight of the body along with its limbs.
- It affords protection to the internal organs against mechanical injury by forming cage-like compartments, e.g., skull.
- It serves as a storage depot for calcium and phosphate, which are released for a number of functions of the body.
- It participates in movement and locomotion.
The spinal nerve in man
(a) Afferent neurons and efferent neurons.
Afferent neurons and efferent neurons:
Afferent neurons: These conduct sensory impulses from the receptors present in the peripheral organs and tissues towards the central nervous system. Their bodies are called afferent neurons.
Efferent neurons: These conduct motor impulses from the central nervous system to the peripheral organs and tissues serving as effectors. Their cell bodies are called efferent neurons.
(b) Rods and cones
Rods: Rod cells are rod-like, elongated cells, bearing long, thin cylinders, containing a visual pigment called Rhodopsin. Rod cells are present on the periphery of the retina in the human eye. These cells do not form color vision.
Cones: Cone cells are shorter, thicker, and conical in shape. These are highly sensitive to bright light and colors. They contain a violet color pigment called rhodopsin. Cone cells are responsible for the perception of different colors. Cones are abundant on the rear wall and fovea centralis of the retina.
(c) Resting membrane potential and action potential.
Resting membrane potential: The surface of the axon carries a positive charge relative to its interior and this electrical potential difference across the plasma membrane is called resting membrane potential.
Action potential: The shift of ions and consequents shift in electrical charges is sufficient enough it will trigger a wave of transient membrane depolarization known as nerve impulse or Action potential.
(d) Impulse conduction in myelinated nerve fiber and unmyelinated nerve fiber.
Impulse conduction in myelinated nerve fiber: The myelinated fibers carry impulses nearly 20 times faster than the non-myelinated nerve fibers. These avoid dissipation of impulse into adjusting fibers. The myelin sheath serves as a highly insulating layer that prevents the flow of ions. Impulses are rapid.
Non-myelinated nerve fiber: Ionic changes and depolarization are repeated over the membrane all along with the fiber. Impulse requires less energy and does not need to run all along with the fiber.
(e) Aqueous humor and vitreous humor.
Aqueous humor: The chamber between the cornea and lens is filled with a clear watery fluid, the aqueous humor.
Vitreous humor The chamber behind the lens is filled with a semisolid gelatinous material the vitreous humor.
(f) Blindspot and yellow spot.
Blindspot: It s a small insensitive light area of about 0.5 cm. in diameter. It is devoid of rod and cone cells. It is unable to receive light rays.
Yellow spot: A tiny circular area, about 6 mm in diameter in the retina is a yellow spot. Here the vision is sharpest. It has rod and cone cells.
(g) Cranial nerve and spinal nerves.
Cranial nerve: There are 12 pairs of cranial nerves, 10 originate from the brain stem, but all pass through the foramina of the skull. Cranial nerves contain only sensory fibers. The remainder contains both sensory and motor fibers.
Spinal Nerve: They arise from the cord. 31 pairs of segmental spinal nerves arise from the cord. They contain both receptor neurons and effectors neurons.
Why is that neurons aren't physically connected?
I know about synapses and neurotransmitters, but why aren't the neurons actually physically connected? Wouldn't it make impulse movement faster? I admit it might, possibly, stop neurons from connecting to more than one or two, but still, why?
Lots of answers, all with some merit.
First of all, some neurons ARE connected. These connections are known as gap junctions. They function like tiny excitatory synapses.
Second, the MAIN difference (IMNSHO) is that synapses are not only connections between neurons. They can be excitatory or inhibitory (gap junctions can not be inhibitory), and they can have ionotropic function, metabotropic function, or both.
In an ionotropic receptor at a synapses, opening the synapse causes excitatory OR inhibitory cyrrent to flow. In a metabotropic receptor, there are cell biological messengers that are triggered by receptor action. You can't have metabotropic actions without synapses. At least not in the same way as far as I know.
It is not that hard to imagine gap junctions changing in strength in a plasticity-type way (there is probably even evidence this happens), and can serve as simple excitatory synapses. But inhibitory current flow and metabotropic actions really only occur at chemical synapses.
It may also be considered a bit of a stretch to call the neurons NOT physically connected when they have a synapse between them. When you consider how it looks under EM, and the exquisite regulations of the membrane scaffolding at the synapse, it is impressive as hell!
Explainer: What is a neuron?
An artist’s drawing of your brain hosting a network of neurons that receives and passes along sensory information. Nerve cells do important work throughout the body.
PIXOLOGICSTUDIO/SCIENCE PHOTO LIBRARY/Science Photo Library/Getty Images Plus
It’s morning. As you sit up in bed, your feet touch the cold floor, so you lift them and put on your socks. In the kitchen, you watch the cereal pour from the box and hear it ping against the bowl. You tip in a stream of milk — carefully — because you spilled it yesterday. All of these experiences are possible because of cells in your brain, called neurons. These cells are dedicated to sensing information in the world around you, then helping you respond to it and learn.
This family of cells send messages to each other, day and night. Along the way, they sense information. They tell other cells what to do. And they remember and respond to what you have learned.
Explainer: What is neurotransmission?
For instance, the smell of burning bread will trigger sensory neurons to send a message to your brain. This neurotransmission then informs motor neurons in your legs and arm muscles to run to the toaster and pop up the smoking toast. Next time you use the appliance, you remember to turn down the heat, because some specialized neurons in your brain have connected to other neurons dedicated to memory.
Sensory and motor neurons are two different classes of neurons. Within these classes are hundreds of different types, each built differently to do a specific job. How all these neurons connect to each other changes from one person to another. That’s what makes each of us unique in how we think, feel and act.
Educators and Parents, Sign Up for The Cheat Sheet
Weekly updates to help you use Science News for Students in the learning environment
What makes these cells special
Neurons have all of the basic features of animal cells. For instance, they have a nucleus and an outer membrane. But unlike other cells, they also have branching hair-like structures called dendrites. These catch chemical messages from other cells. The dendrites send each impulse to the main part of the cell. It’s known as the cell body. From there, the signal moves along a long thin section of the cell called the axon. This electrical impulse is made by waves of charged particles weaving in and out of the cell membrane, rippling the signal along. Some axons have fatty rings of myelin (MY-eh-lin) on them, lined up like beads on a string. When the neurons are myelinated, the message will bounce along much faster.
The message leaves an axon through finger-like terminals at the end. Chemicals released out of the cell here will then be picked up by the dendrites on a neighboring cell. The area from one cell’s terminals, across the gap between cells and on to the next cell’s dendrites is known as a synapse (SIH-napse). Messages pass between one cell and onto the next by floating across the space between — a gap called the synaptic cleft. This tiny space between the two cells is filled with fluid. In the next neuron, the chemical signals enter molecules called receptors like a key into a lock.
Anatomy of a Neuron
Dendrites branch out from the head (cell body) of a neuron. They receive chemicals which serve as a message. When one arrives, it moves into the cell body. From there, it travels as an electrical impulse down the axon to its terminals. Those terminals will release packets of chemical messengers, passing on the signal to a neighboring neuron’s dendrites.
Vitalii Dumma/iStock/Getty Images Plus
Neurons in your brain relay messages across synapses and on through chains and webs of additional cells. They transmit messages in much the same way that data move from computer to computer through the internet.
Scientists who study the brain — neuroscientists – work to understand the connections and messaging between neurons. They use wires and magnets outside or inside the body to measure signals that pass through nerve cells. This works because the messages are ions, molecules with positive and negative electrical charges. The fluid inside and between all those neurons is made of these charged chemicals.
Neighboring neurons may not always be close by. In the body, a single nerve cell can extend a pretty long axon — up to the length of your leg. Your brain and spinal cord, however, are masses of branching networks of small neurons. They have the support of other cells called glia. Glial cells protect, support, feed and do cleanup for the neurons. Think of them as the support crew for neurons.
Many cells in your body are replaced daily, such as stomach and skin cells. But neurons live a long time. In many cases, they are as old as you are. Scientists are still figuring out when and where neurons first appear as your body develops. They know they form from areas in the body rich with super-powered cells, called stem cells. After neurons develop, they travel to different positions and start connecting to form networks.
axon: The long, tail-like extension of a neuron that conducts electrical signals away from the cell.
cell: The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
cell body: The compact section of a neuron where its nucleus is located.
chemical: A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
dendrites: Hair-like projections from the head (cell body) of a neuron. They sit ready to catch a neurotransmitter, a chemical signal, that has been released by a neighboring neuron.
develop: To emerge or to make come into being, either naturally or through human intervention, such as by manufacturing. (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size, mental maturity or sometimes even shape.
glia: Support cells for neurons. The human brain has about 86 billion of these glial cells. Some of them wrap around axons and produce a fatty cover. This speeds the rate of neural signaling and helps prevent confusing “cross-talk” between neighboring neurons. Other glial cells provide nutrients and support to neurons and guide new neurons to their destinations.
host: (in biology and medicine) The organism (or environment) in which some other thing resides. (v.) The act of providing a home or environment for something.
internet: An electronic communications network. It allows computers anywhere in the world to link into other networks to find information, download files and share data (including pictures).
ion: (adj. ionized) An atom or molecule with an electric charge due to the loss or gain of one or more electrons. An ionized gas, or plasma, is where all of the electrons have been separated from their parent atoms.
magnet: A material that usually contains iron and whose atoms are arranged so they attract certain metals.
membrane: A barrier which blocks the passage (or flow through) of some materials depending on their size or other features. Membranes are an integral part of filtration systems. Many serve that same function as the outer covering of cells or organs of a body.
model: A simulation of a real-world event (usually using a computer) that has been developed to predict one or more likely outcomes. Or an individual that is meant to display how something would work in or look on others.
motor neuron: A cell that’s part of a pathway through which impulses pass between the brain or spinal cord and a muscle (or gland).
muscle: A type of tissue used to produce movement by contracting its cells, known as muscle fibers. Muscle is rich in protein, which is why predatory species seek prey containing lots of this tissue.
myelin: (also as in myelin sheath ) A fatty layer that wraps around the axons of neurons. This cover, or sheath, made from glial cells, insulates the axons of these neurons, speeding the rate at which signals speed down them.
nerve: A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.
nervous system: The network of nerve cells and fibers that transmits signals between parts of the body.
network: A group of interconnected people or things. (v.) The act of connecting with other people who work in a given area or do similar thing (such as artists, business leaders or medical-support groups), often by going to gatherings where such people would be expected, and then chatting them up. (n. networking)
neuron: An impulse-conducting cell. Such cells are found in the brain, spinal column and nervous system. Neurons outside the brain are usually referred to as nerve cells.
nucleus: Plural is nuclei. (in biology) A dense structure present in many cells. Typically a single rounded structure encased within a membrane, the nucleus contains the genetic information.
spinal cord: A cylindrical bundle of nerve fibers and associated tissue. It is enclosed in the spine and connects nearly all parts of the body to the brain, with which it forms the central nervous system.
stem cell: A “blank slate” cell that can give rise to other types of cells in the body. Stem cells play an important role in tissue regeneration and repair.
synapse: The highly localized region over which neuron communications occur. It includes the ends of axons that release a type of chemical signal. It includes the short gap over which that chemical travels to reach the next neuron. And it includes the ends of the dendrites on a neighboring neuron that stand waiting to receive the chemical message.
transmit: (n. transmission) To send or pass along.
unique: Something that is unlike anything else the only one of its kind.
Key Pathway In Synaptic Plasticity Discovered
Scientists are keenly studying how neurons form synapses--the physical and chemical connections between neurons--and the "pruning" of neural circuits during development, not least because synaptic abnormalities may partially underlie many developmental and neurodegenerative diseases.
Several key molecules are involved in normal synaptic formation, but their interactions are not well understood. Now MIT neuroscientists have taken an important step toward solving this challenging jigsaw puzzle. They have pieced together a direct linear pathway connecting three molecules involved in synaptic formation, to be reported in the May 21 advance online publication of Nature Neuroscience.
"We haven't solved the whole puzzle yet," cautions Martha Constantine-Paton, a developmental neuroscientist in the McGovern Institute for Brain Research at MIT, professor in the Department of Biology and senior author of the paper. "But we do now have a broader view of what happens in synaptic plasticity (adaptability). More importantly, we have an exciting model of this new pathway's role in development and learning. We hope this study might advance the study of normal, healthy brain development in people so that we may be able to prevent or treat many devastating developmental neurological disorders."
Constantine-Paton and her co-author, Akira Yoshii, a pediatric neurologist and research scientist in her lab, use the rodent visual pathway as an accessible model for studying how the signaling properties of synapses change during development and how those changes relate to structural changes in the brain and developmental milestones in behavior.
Specifically, they focus on a major developmental event-eye opening, which in rodents happens after birth and is followed by rapid increases in synapse strength and visual circuit refinement that follow the onset of visual stimulation. Previously, the authors had discovered a possible mechanism for that increase in synaptic strength. Namely, a protein called PSD-95 rushes to the synapses within hours of eye opening. PSD-95 is a scaffold that anchors, among other things, two classes of receptors for the neurotransmitter glutamate, which triggers the cell's electrical activity during development and learning. Curiously, PSD-95 also held the receptor for BDNF (TrkB), an important factor that is necessary for synaptic strengthening during development and learning.
In the current work, the researchers set out to explore the relationship between BDNF and PSD-95. In so doing, they defined an entirely new pathway that may explain an intriguing phenomenon in development.
In short, stimulating visual neurons initiates a positive feedback loop, starting with one class of glutamate receptors known as NMDA receptors, which activate BDNF. BDNF triggers a signaling pathway involving another well-studied duo, PI3 kinase/AKT. That pathway causes more PSD-95, and with it more receptors for BDNF, to accumulate at the synapse within one hour of stimulation. As a result, the synapse becomes more responsive to BDNF, which sends more PSD-95 to the synapse.
Surprisingly, stimulating just a few synapses with BDNF sends more PSD-95 to excitatory synapses throughout the entire neuron within the hour. This newly described pan-neuron effect of local synaptic stimulation is similar to "synaptic tagging," which is a mechanism originally proposed to explain how a few very active synapses can prime larger regions of a neuron for long-term synaptic strengthening in response to subsequent stimulation.
"A mechanism like the BDNF/PSD-95 pathway could account for numerous observations at the cellular level in animal models, or during behavioral development in young children," explains Yoshii. "Namely, the development of particular neurological connections or skills does not occur gradually over time. Instead such changes tend to occur suddenly, appearing in short intervals after robust stimulation. It is as if there is a single important trigger and then a functional circuit rapidly comes online."
This work was funded by the National Eye Institute of the National Institutes of Health.
What prevents neurones from touching at chemical synapses? - Biology
C2006/F2402 '08 Outline for Lecture 15 -- (c) 2008 D. Mowshowitz -- Lecture updated 03/26/08 .
Handouts: 15B (bottom) Circuits 15B (top) CNS/PNS 15A is not on line -- has diagrams for summation and for sensors. Extra copies of class handouts are in boxes outside Dr. M's office 7th floor Mudd.
Added 3/26 : An extensive discussion of the role of the receptor (in determining the response) was included in the live lecture, but not in the notes below. The example used was the response to epinephrine. Notes on this are posted as Supplement to Lecture 15.
Note on refractory periods: T here is some disagreement between authorities on the timing of the refractory periods. According to handout 13A, and to Becker, the absolute refractory period comes right after the spike of the action potential. According to some, the absolute refractory period coincides more or less with the spike the relative refractory period follows after the spike. All agree about the underlying mechanism. The absolute refractory period corresponds to the time when the Na + channels are inactivated (so depolarization is not possible). The relative refractory period corresponds to the time when the Na + channels can be activated, but the voltage gated K + channels are still open (so depolarization to threshold requires a larger stimulus).
A few Interesting links:
1991 Nobel Prize in Medicine for Patch Clamping (Neher & Sakmann)
1936 Nobel Prize in Medicine for Chemical Nature of Transmission at Synapses (Dale & Loewi)
1994 Nobel Prize in Medicine for discovery of G proteins (Gilman & Rodbell)
Two more animations by Steve Berg: Action Potential and Voltage gated cation channel.
I. Nerve-Nerve Synapses, cont. -- What determines if a nerve impulse will be passed on to the next neuron? For nice overall pictures see Sadava 44.13 or Becker fig. 13-19 & 13-21 (9-21 & 9-23). Some of this is review, but is included for clarity.
A. Presynaptic Side -- Transmitters -- See Sadava Table 44.1 & Becker fig. 13-20 (9-22).
1. One major type of transmitter per synapse (released from pre-synaptic side)
a. In CNS , many diff. transmitters. Usually amino acids or their derivatives. Major ones are glutamate (excitatory) & GABA (inhibitory).
b. In PNS usually norepinephrine (NE) or acetyl choline (AcCh).
2. One transmitter per Neuron. Usually only one major transmitter released by any neuron. Therefore one major transmitter released -- the same one -- at all synapses made by that neuron.
3. Release of Transmitter:
a. Location of Transmitter: Neurotransmitters are in vesicles (except for gaseous NTs)
b . Trigger for release: Action potential (AP) stimulates Ca ++ channel opening in plasma membrane, raising intracellular Ca ++
c. Exocytosis: High intracellular Ca ++ promotes exocytosis and release of transmitter.
4. Effects of transmitter (on target) can vary. Some transmitters are always excitatory or inhibitory other transmitters vary in effect (depends on if you have one or more type of receptor for that transmitter -- see below.)
5. Getting rid of transmitters
a. Transmitter doesn't remain in synaptic cleft for long.
b. Different methods for getting rid of dif. transmitters
(1). Diffusion away from cleft
(2). Destruction by enzymes in cleft. For ex, acetyl choline esterase (AcChE) in cleft breaks up AcCh (Choline is reused). See Sadava fig.44.14
(3). Reuptakeby transporters (secondary active transport) -- NE, serotonin removed from cleft by reuptake. (Endocytosis recovers membrane transporters recover transmitters.)
c. Many drugs affect release/fate of transmitters for ex.
(1). Prozacprevents serotonin reuptake -- transmitter stays around longer → more stimulation.
(2). Malathion (insecticide) & nerve gas block AcChEsterase → continuous stimulation → spasms
B . Post Synaptic Side -- PSP's = post synaptic potentials = small change in potential due to release of transmitter
1. Can be inhibitory (NT generates an IPSP) or excitatory (NT generates an EPSP)
a. Inhibitory -- causes hyperpolarization or stabilizes existing negative polarization due to opening of K + or Cl - channels. Either K + goes out or Cl - comes in.
b. Excitatory -- causes depolarization due to opening of cation channels Na + in>> K + out.
c. Terminology -- a single IPSP or EPSP usually refers to the small change in potential due to release of transmitter caused by a single AP. The total PSP depends on the algebraic sum of multiple IPSP's and EPSP's as explained below.
2. Any given synapse is excitatory or inhibitory -- What determines it?
(1). One type of receptor for neurotransmitter at each synapse.
(2). Receptor determines which kind of synapse it is -- excitatory or inhibitory.
(3). Same neurotransmitter can be excitatory or inhibitory at different synapses.
(4). Receptor can be
(a) ionotropic (direct) -- receptor is itself an ion channel. Faster response Ligand binding always opens channel. For examples see Sadava 44.17 or Becker 13-23 (9-25). Also see many pictures in both books of neuromuscular junction, or handout 13.
(b) metabotropic (indirect) -- receptor uses GPCR & 2nd messenger. Response is slower, but effects can be more varied & more extensive. Can be used to open or close ion channels. See Sadava 44.16.
(5) Agonists and antagonists are used as common tools to study receptors for both NTs and hormones. Some receptors named by their common ligand and most common agonist or antagonist. (For example, the nicotinic acetyl choline receptor. Ac Ch = NT nicotine = agonist.) For more examples, see table at end of notes.
b. Overall: One receptor/neurotransmitter pair per synapse.
3. Features of Total PSP's (To compare to AP's)
a. Total PSP's are graded -- size is proportional to stimulus (as with receptor potentials, see below). Size is not all or none. (Unlike action potentials.)
b. PSP's are local -- die out if don't reach threshold. (Not regenerated like AP's.)
c. PSP's are caused by opening/closing of ligand gated channels. (What kind of channel is needed for AP's?)
To review IPSP's and EPSP's try problem 8-10.
C. Post Synaptic Side -- Summation -- See Sadava fig. 44.15 or Becker 13-24 (9-26 & 9-27).
1. Inputs (IPSP's & EPSP's) to cell body/dendrites are summed -- changes spread around cell body to initial segment (or die out).
2. No AP in cell body. No voltage gated channels in cell body so no AP generated there
3. Axon Hillock. Voltage gated channels begin at initial segment (also called the "trigger zone" or axon hillock) so AP starts there. See Becker fig. 13-14 (9-16) or Sadava 44.15.
4. Inputs summed over space and/or time -- need to depolarize past threshold at axon hillock to → AP. See handout 15A, bottom.
a. Spatial summation: Multiple EPSP's delivered at different spots can add up → AP
b. Temporal summation: Multiple EPSP's delivered close enough together in time can add up → AP
c. Why you need summation:
(1). A single EPSP is not enough to → AP
(2). IPSP's & EPSP's are summed: net effect depends on both inhibitory and excitatory input. Remember there are about 1000 synapses (inputs) on body & dendrites of average neuron. See Becker fig. 13-24 (9-27). (See circuits below for how you use this.)
Review Problem 8-8, parts A to H, and recitation problem 8-2.
II. Sensors See Handout 15A (top). Sadava has a whole chapter on Sensory Systems. (Chapter # depends on which edition of the text you have.) Only a few general principles discussed here. See Sadava for examples & details.
A. The Problem: How does a small stimulus (from the environment) reach the nervous system?
1. The Question: Where does input come from, if not from another neuron? How do you get input from the environment -- from sight, sound, etc. -- and send it to the CNS?
2. The Short Ans :
Touch, hearing, etc., produce a small response = change in polarization by opening/closing channels in special cells (receptor cells or sensors).
Change in opening of channels (& therefore change in polarization) is proportional to stimulus.
The small change in polarization opens voltage gated channels which generates a big response -- an AP. (The 'big bang' or the 'toilet flush,' so to speak.) See left-most case on the 'big bang' handout.
1. Special (Sensory) cells contain receptor proteins for stimuli (pressure, light, heat, chemicals, etc.).
2. How do protein receptors detect stimuli?
a. Stimuli → Change in conformation of receptor → open or close channels in membrane → change in polarization of membrane.
b. How are channels opened or closed? See Sadava 45.1.
(1) Directly -- receptor is part of a channel = an ionotropic receptor. Examples: receptors for mechanical stimuli (touch, hearing, balance), & temperature (heat/cold). Receptor changes shape and channel opens.
(2) Indirectly -- receptor is not part of a channel = a metabotropic receptor. Change in conformation of receptor activates a G protein. G protein or 2nd messenger opens/closes channel. Examples: receptors for chemicals (taste, smell, etc.), electromagnetic radiation (vision).
C. Receptor Potentials
1. Response to stimulus is graded. Stimulus → local graded response. The more stimulus, the more channels open (or close), and the bigger the graded potential (bigger depolarization or bigger hyperpolarization) in the sensory/receptor cell.
2. Terminology -- graded response in receptor/sensory cell is called a generator potential or receptor potential.
D. Receptor Cells. Two types of Sensory Cells (aka receptor cells) = special cells with molecular receptors for detecting stimuli
1. Modified neuron -- sensory cell is a modified neuron capable of generating AP itself. (See Sadava 45.2 & below for an example.)
2. Cell that cannot generate an AP itself
a. How get an AP? Sensory cell releases transmitter and triggers AP in next cell (a neuron). See Sadava 45.5 for an example.
b. Type of cell. This type of sensory cell can be a modified neuron or epithelial cell.
Question to ask yourself: What type of channels does a cell need in order to generate an AP?
E. How Does Graded response generate an AP? -- Note there are two issues here: How many cells? (Either one or two) and whether receptor is ionotropic (direct) or metabotropic (indirect). See handout 15A.
1. AP is in modified neuron -- one cell system. Graded potential (generator potential*) triggers AP in same cell (if stimulus is over threshold) → input to CNS.
a. Example #1 -- direct (ionotropic receptor) -- stretch. Sadava 45.2 for example.
Stimulus = stretch on nerve endings → open channels → depolarize to threshhold → AP (in sensor cell itself).
b. Example #2 -- indirect (metabotropic receptor) -- smell (olfaction). See Sadava 45.4.
Stimulus = Ligand (odorant) → Receptor → G protein → adenyl cyclase → cAMP up → open cation channel (cyclic nucleotide gated channel) → depolarize cell → AP.
Question: Where will the action potential start? In what part of the cell? See Sadava 45.2
2. AP is in separate (post-synaptic) cell -- two cell system
a. Graded potential (receptor potential*) triggers release/inhibition of transmitter by receptor/sensory cell.
b. Amount of transmitter released by sensory cell is proportional to stimulus.
c. Transmitter generates IPSP or EPSP in neuron (next cell = post synaptic cell).
d. Transmitter triggers AP in post synaptic neuron if stimulus is over threshold → input to CNS.
e. Examples: vision & taste (indirect) balance & hearing (direct).
* In older editions of Sadava, the terms "generator potential" and "receptor potential" are used to refer to these two different cases respectively. Most texts stick to "receptor potential" or use the two terms interchangeably.
Which type of receptor cell are you dealing with in problem 8-16?
F. All stimuli (whatever the modality) give same message to CNS (= AP's). If AP is all or nothing, how do you know which stimulus it was? And how much?
1. Number, frequency of AP's indicate length (duration) and strength (intensity) of stimulus.
2. Wiring (what part of brain is stimulated) = labeled lines = indicates location of stimulus and type (modality) of stimulus -- taste, stretch, etc. If you get a punch in the eye, you set off light receptors. For a less violent example, take a very sharp pencil and tap your upper lip. What sensors did you trip off? (For contrast, tap your arm.)
To review sensors, try Problem 8-16 . To review electrical communication overall, try 8-15.
III. Circuits - - how nervous system is organized
A. Simple circuits -- see handout 15B, bottom or Sadava 46.3
1. One synapse, 2 neurons -- monosynaptic circuit -- how sensory neuron signals an effector.
Live Lecture got to here. Rest will be covered next time.
2. Circuit with multiple synapses -- how antagonistic muscles are controlled. (Signal to skeletal muscle is always + a signal (+) means contract no signal means relax.)
3. Role of brain -- adds up/down (as vs. in/out) component
4. FYI: Where is all this located? see Sadava 46.3 will not be discussed in class.
B. How is NS organized overall? See handout 15 B, Becker 13-1 (9-1) or Sadava 46.1
a. CNS = brain + spinal cord
b. Interneurons. Most neurons of CNS are interneurons (99%)
c. White matter = axons
d. Grey matter = cell bodies, interneurons, and dendrites
2. PNS -- Names of Divisons
a. Afferent vs Efferent.
(1) Afferent = carrying info into the CNS
(2) Efferent = carrying info away from the CNS
b. Efferent subdivided into: Somatic vs autonomic
(1) Somatic = controls skeletal muscle
(2). Autonomic = controls everything else
c. Autonomic subdivided into: Parasympathetic (PS) vs Sympathetic (S)
Try problem 8-8, part I.
C. How do PS and S co-operate? (See Sadava 46.10) What do they do?
1. What do they innervate?
a. Many organs innervated by both
b. Some organs innervated (stimulated) by only one
(1). liver, sweat glands -- S only
(2). tears -- PS only
2. What results does stimulation produce?
a. Not always S excites PS inhibits. Ex: salivation -- S inhibits PS excites
(1). S → response needed in a crisis
(2). PS → response needed in relaxed state.
(1). S → heart rate up liver releases glucose bladder relaxes (to hold more)
(2). PS → heart rate down, digestion, salivation up.
D. General Set up of wiring of efferent PNS -- see handout 15A (Any details not done today will be done next time.)
1. First neuron -- same in Somatic and Autonomic.
a. Location -- body in CNS
b. Neurotransmitter -- releases AcCh
c. Receptor -- AcCh receptor (on effector/next neuron) is nicotinic
2. Second neuron (post ganglionic) -- found in autonomic only
a. Location -- Body in ganglion
(1). Parasympathetic -- releases AcCh
(2). Sympathetic -- usually releases NE
c. Receptor (on effector)
(1). AcCh (cholinergic) receptor is muscarinic
(2). NE (adrenergic) receptor can be alpha or beta (see table below)
d. Adrenal medulla ≡ second neuron. Medulla composed of many neurons with short axons. Release neurotransmitter (mostly E) from end of short axons (within medulla). E goes into blood, so E acts as neuroendocrine instead of neurotransmitter.
Try problem 8-8 part J.
E. Major Types of Receptors in the PNS -- Reference & summary
Neurons are not joined up together. There are small gaps between one neuron and the next, more like switches.
The gaps between neurons are called Synapses. When an impulse reaches the synapse, a conducting chemical called a neurotransmitter is released. This allows the impulse to pass through the gap. After the impulse has passes, the neurotransmitter is broken down and reabsorbed.
Unfortunately, because the neurotransmitter has to diffuse across the gap/synapse, it results in a small delay of about 0.2 milliseconds. Not much, is it? Since there are many more synapses along the route of the impulse, the delay accumulates and becomes substantial.
The Reflex pathway
A Reflex is a quick, automatic response to a stimulus. It does not need you to think, you just do it. Ever said 'that was a knee-jerk reaction'?
- Yes a knee jerk is a reflex, so is:
- Removing your hand from a hot Bunsen
Why do we need reflexes?
If we had to think about the response, it would take too long to react and damage our affected body part or even get us killed. This is because of many synapses that the impulse will need to cross causing a significant delay.
Reflex arc/pathway- is the order of neurons that the impulse follows during a reflex action. In simple terms, this is:
Receptor- Sensory Neuron- Relay Neuron- Motor Neuron- Effector
Just memorise this and you will be ok for exams.
Why is a chemical synaptic transmission unidirectional? Does calcium open up Ca+ channels in the bulb and Ca+ rushes in and allows for neurotransmitters to enter?
Synaptic transmission is undirectional because neurotransmitters cannot be exchanged otherwise.
A synapse is a link between two neurons in our bodies. The synapse is showed schematically below.
A synapse has a side which releases neurotransmitters and a side that can receive them. When a signal travels towards such a synapse, these neurotransmitters are released in the synaptic gap and can travel free around. If such a neurotransmitter is bonded to a receptor on the other site of the synaptic gap, this releases another signal which travels further and further in our body.
We see now, that these neurotransmitters cannot cause a signal to go backwards. The receptor site cannot release them and the synaptic knob cannot receive them.
For your interest, neurotransmitters are mostly broken down in the synaptic gap after they are released, so another signal can come through!
There are two types of effects caused by neurotransmitters: excitation and inhibition. Inhibition is when a molecule lowers the potential to create a new electrical signal and excitation is when a molecule raises the potential to create a new electrical signal output.
Why is it important to have a unidirectional unit in our nerve system?
This is because all the other neurons do not have a specific direction. Image what a chaos would be created if everything gets triggered and triggered because there is no way you can stop a signal!
What has calcium to do with this?
Calcium is part of the system that releases the neurotransmitters in the synaptic cleft. If an electric signal reaches the synapse, membrane ports are put open and calcium is transferred into the synapse, creating a high concentration inside (see image below). Specific proteins on the membrane of the neurotransmitter carrier (the bubbles) react on this higher concentration and fuse with the cell membrane, releasing the neurotransmitters in the synaptic cleft.
Functions of the Cortex
When the German physicists Gustav Fritsch and Eduard Hitzig (1870/2009) applied mild electric stimulation to different parts of a dog’s cortex, they discovered that they could make different parts of the dog’s body move. Furthermore, they discovered an important and unexpected principle of brain activity. They found that stimulating the right side of the brain produced movement in the left side of the dog’s body, and vice versa. This finding follows from a general principle about how the brain is structured, called contralateral control. The brain is wired such that in most cases the left hemisphere receives sensations from and controls the right side of the body, and vice versa.
Fritsch and Hitzig also found that the movement that followed the brain stimulation only occurred when they stimulated a specific arch-shaped region that runs across the top of the brain from ear to ear, just at the front of the parietal lobe (see Figure 3.11 “The Sensory Cortex and the Motor Cortex”). Fritsch and Hitzig had discovered the motor cortex , the part of the cortex that controls and executes movements of the body by sending signals to the cerebellum and the spinal cord. More recent research has mapped the motor cortex even more fully, by providing mild electronic stimulation to different areas of the motor cortex in fully conscious patients while observing their bodily responses (because the brain has no sensory receptors, these patients feel no pain). As you can see in Figure 3.11 “The Sensory Cortex and the Motor Cortex”, this research has revealed that the motor cortex is specialized for providing control over the body, in the sense that the parts of the body that require more precise and finer movements, such as the face and the hands, also are allotted the greatest amount of cortical space.
Figure 3.11 The Sensory Cortex and the Motor Cortex
The portion of the sensory and motor cortex devoted to receiving messages that control specific regions of the body is determined by the amount of fine movement that area is capable of performing. Thus the hand and fingers have as much area in the cerebral cortex as does the entire trunk of the body.
Just as the motor cortex sends out messages to the specific parts of the body, the somatosensory cortex , an area just behind and parallel to the motor cortex at the back of the frontal lobe, receives information from the skin’s sensory receptors and the movements of different body parts. Again, the more sensitive the body region, the more area is dedicated to it in the sensory cortex. Our sensitive lips, for example, occupy a large area in the sensory cortex, as do our fingers and genitals.
Other areas of the cortex process other types of sensory information. The visual cortex is the area located in the occipital lobe (at the very back of the brain) that processes visual information. If you were stimulated in the visual cortex, you would see flashes of light or color, and perhaps you remember having had the experience of “seeing stars” when you were hit in, or fell on, the back of your head. The temporal lobe, located on the lower side of each hemisphere, contains the auditory cortex , which is responsible for hearing and language. The temporal lobe also processes some visual information, providing us with the ability to name the objects around us (Martin, 2007).
As you can see in Figure 3.11 “The Sensory Cortex and the Motor Cortex”, the motor and sensory areas of the cortex account for a relatively small part of the total cortex. The remainder of the cortex is made up of association areas in which sensory and motor information is combined and associated with our stored knowledge. These association areas are the places in the brain that are responsible for most of the things that make human beings seem human. The association areas are involved in higher mental functions, such as learning, thinking, planning, judging, moral reflecting, figuring, and spatial reasoning.
Whilst stimulants alter the effects of neurotransmitters by blocking re-uptake, tranquillisers and barbiturates affect neurotransmitters in another way.
Tranquillisers, barbiturates and alcohol are part of a class of drugs known as depressants. These drugs produce their depressive effects on the brain by mimicking the neurotransmitter known as GABA-A.
Alcohol affects GABA-A ion channels by causing these channels to leak excess negative ions into the neurons. This causes these neurons to fire less frequently.
Tranquillisers and barbiturates also cause more negative ions to leak through GABA-A channels but do so in a different way. These drugs bind to receptor sites on the GABA-A channel just like the real GABA-A neurotransmitter molecules.
By doing so, these drugs cause the GABA-A channels to open more often and for longer periods of time. The result is that more negative ions enter the neuron causing less brain activity. This is why people under the influence of these drugs tend to slur their speech.
What prevents neurones from touching at chemical synapses? - Biology
The adult C. elegans hermaphrodite has 302 neurons that belong to two distinct and independent nervous systems: a large somatic nervous system (282 neurons) and a small pharyngeal nervous system (20 neurons). These systems communicate through a single pair of RIP interneurons (NeuroFIG 1) (Ward et al., 1975 Sulston and Horvitz, 1977 Sulston et al., 1983 White et al., 1986). (For a discussion of the pharyngeal nervous system, see Alimentary System - Pharynx ) The two nervous systems differ in their topologies. In the somatic nervous system, the neurons and their processes are generally positioned between the hypodermis and the body wall muscle and share a basal lamina with the hypodermis that isolates them from the muscles (NeuroFIG 2). In contrast, the pharyngeal neurons lie directly among the pharyngeal muscles and are not separated from their muscle targets by a basal lamina. The neurons in the hermaphrodite have been assigned to 118 distinct classes according to their topology and synaptic connection patterns (White et al., 1986). Cell bodies of most neurons are clustered in ganglia in the head or tail (NeuroFIG 1). C. elegans has 56 neuronal support cells (including the GLR cells see Muscle System - GLR Cells), which are associated only with the somatic nervous system. The neurons communicate through approximately 6400 chemical synapses, 900 gap junctions, and 1500 neuromuscular junctions (NMJs). Among individual animals, the location of chemical synapses is about 75% reproducible (Durbin, 1987). Every C. elegans neuron name consists of either two or three uppercase letters indicating class and in some cases a number indicating the neuron number within one class. If the neurons are radially symmetrical, each cell has a three-letter name followed by L (left), R (right), D (dorsal), or V (ventral). A complete list of C. elegans neurons, their lineage, and descriptions can be found in the Individual Neuron section of the WormAtlas.
Males have a larger nervous system with 473 cells (with an additional 79 neurons and 36 support cells). Most of these extra, male-specific cells are involved in male mating behavior and are located in the posterior body (Sulston et al., 1980 Lipton and Emmons, 2003 Emmons, 2005). The four CEM (cephalic neuron in male) neurons are an exception they are located in the head as part of the male cephalic sensilla. The hermaphrodite has only two classes of hermaphrodite-specific neurons: HSN, which are generated in males but go through programmed cell death during early development, and VC neurons, which are derived from the P lineages that give rise to cells of the hook sensillum in males. All of the neurons in both sexes have been individually identified and their lineages described. The connectivity among the hermaphrodite neurons has been established from electron micrographs of serial thin sections, whereas the connectivity of the male nervous system has been the focus of more recent studies (Ward et al., 1975 Ware et al., 1975 White et al., 1986 Durbin, 1987 Hall and Russell, 1991 Chen et al., 2006 see also Male Anatomy.
Despite its compact nervous system, C. elegans is capable of several complex behaviors, in addition to the basics such as locomotion, foraging, feeding, and defecation (de Bono and Maricq, 2005). The animal can discriminate and move toward or away from chemicals, odorants, temperatures, and food sources. It can also detect the presence, density, and sex of nearby nematodes by short-range diffusible signals, by a pheromone, and by changes in oxygen levels (Riddle and Golden, 1982 Cheung et al., 2004 Gray et al., 2004 Jeong et al., 2005 Barr and Garcia, 2006). The animal displays social feeding behavior (de Bono, 2003). Each sex also displays sex-specific behaviors such as egg-laying in hermaphrodites and mating behavior in males (Schafer, 2005). Most of these behaviors are plastic and therefore subject to change through learning and memory (Giles et al., 2006). Additionally, food is a significant modulator of many C. elegans behaviors, including egg-laying, feeding, locomotion, and olfactory behavior, often through serotonin-dependent pathways (Zhang et al., 2005). The neuron circuits that are dedicated to each of these behaviors may communicate via interneurons to produce hierarchies in their execution. For example, in stressful environments where food is scarce, egg-laying behavior is suppressed, whereas after an encounter with food, locomotion behavior becomes suppressed in a starved animal, allowing the animal to feed properly.
Almost all C. elegans neurons have simple monopolar or bipolar morphologies with mostly unbranched processes that follow nearly identical trajectories in each animal (NeuroFIG 3). A few motor neurons, including VC4 and HSN neurons, make several simple branches as they reach their muscle targets. PVD and FLP neurons are unique in C. elegans because they branch extensively near each body muscle quadrant after early larval stages. Many neurons in the adult male tail are also more highly branched within the preanal ganglion, where some neurons can have four to eight separate branches within the neuropil (S.W. Emmons, J.E. Sulston, D.G. Albertson, M. Xu, and D.H. Hall, unpubl.). Some neuron processes may have pure sensory functions (a dendrite) or pure synaptic output functions (an axon), but many have mixed functions capable of both receiving inputs and sending outputs (a neurite or process).
Neuronal somata are among the smallest in the nematode. In transmission election microscopy (TEM) sections, they are seen as having relatively lightly staining cytoplasm, with a compact nucleus, distinctive rough endoplasmic reticulum (RER), several mitochondria, small clusters of synaptic vesicles, and one or more Golgi bodies. Most of the neuronal nucleus is filled with light-staining &ldquoeuchromatin,&rdquo with a modest amount of dark &ldquoheterochromatin,&rdquo and one or more small round nucleoli. Under differential interference contrast (DIC) microscopy, neuronal nuclei can easily be distinguished as small, stippled ovals (NeuroFIG 1). The processes of individual neurons are generally very thin (100&ndash200 nm in diameter), but show local swellings with clusters of vesicles at synaptic regions along the length of the process (White et al., 1986). Within each neurite or major side branch, a small bundle of microtubules (MTs) runs continuously along its length. In addition, each neurite contains a small tube of smooth endoplasmic reticulum (ER) and occasional mitochondria. A few small clusters of free ribosomes sometimes lie within the neurite not far from synapses, either on the presynaptic or post-synaptic side (Rolls et al., 2002). The exact position of synaptic swellings or short side branches is not identical among animals however, the polarity, handedness, and position of a cell&rsquos main processes are very predictable.
2.1 Nervous System Development
2.1.1 Cell Birth, Programmed Cell Death and Cell Migration
C. elegans neurons are generated at three main developmental periods. The first is during the proliferation phase of embryogenesis, the second at the late-L1 stage, and the third at the L2 stage (Sulston and Horvitz, 1977 Sulston et al., 1983). At the time of hatching, the hermaphrodite worm has 222 neurons (202 somatic, 20 pharyngeal) and most of these derive from the AB lineage (the male worm has 224 neurons at this stage). All of the glial cells arise from the AB lineage. MS (six neurons) and C (two neurons) lineages contribute only a few neurons to the nervous system. During late L1, five classes of ventral nerve cord (VNC) motor neurons are generated from P and W lineages (see Postembryonic Neurons Table). Also at this time, additional neurons are generated from Q, G1, H2, T, and K lineages. In the L2 stage, the G2 blast cell divides to give rise to the excretory socket cell and RMF neuron pair, and V5paa generates the cells of the posterior deirids on both sides (see Epithelial system - Hypodermis). In males, the additional neurons that function in male mating are born during the L3 stage (Sulston et al., 1980). As a general rule in C. elegans neurogenesis, most bilaterally symmetric pairs of neurons arise from bilaterally symmetric cell lineages, but there are exceptions to this rule.
C. elegans uses programmed cell death in two contexts during neurogenesis: to generate sexual dimorphism in certain parts of the nervous system (death of CEM cells in the hermaphrodite and HSN cells in the male) and to eliminate extra motor neuron production in the VNC. The ap daughters of P3a&ndashP8a become VNC motor neurons, whereas the corresponding cells in the other P lineages die (see Epithelial system - Hypodermis). Similarly, P11aaap and P12aaap are eliminated instead of becoming additional VB cells (Sulston, 1976).
Developmentally, neuronal cell movements can be divided into early mass migrations and later individual cell migrations. During embryogenesis, mass neuroblast movements occur to close the ventral cleft (at
230&ndash290 min after first cell cleavage), and they also occur later at comma stage when anterior neuron groups move toward the tip of the head to form rudiments of the head sensilla (see Epithelial system - Hypodermis). During this time, a sensory depression forms at the tip of the head and later everts. The cell bodies of head sensilla later migrate posteriorly, leaving their dendritic processes stretching behind as attached to the lips. Subsequently during elongation, the head neurons are pushed aside as the pharynx grows forward through the mass of neurons surrounding the developing nerve ring (NR). By late embryogenesis, the neurons around the NR settle into their recognizable positions. In later stages, despite the mechanical force generated by body movements, the organization of cells in head ganglia is mostly maintained through homophilic and heterophilic interactions of cell adhesion molecules expressed on the surfaces of the neurons (Sasakura et al., 2005). There are some exceptions to this however in live animals, cells can sometimes be seen to flip from one side of the anterior bulb to the other as the pharynx moves (Z. Altun, unpublished observations White et al., 1986).
Although relative positions of cell bodies within ganglia are fairly well conserved between animals of the same developmental stage and genotype, there is still a certain amount of natural variation. These fall into four groups (Z. Altun, unpublished observations Bargmann and Avery 1996):
1- posterior lateral ganglia neurons (e.g. AIN, RIC, AIZ, ADEso, AVD)
2- postembryonic neurons in the tail (e.g. PHC, PLN, PVN, PVW)
3- postembryonic neurons in the ventral cord (ASn, VAn, VBn, VCn, VDn)
4- the anterior socket and sheath cells in the head, such as ILsh, ILso, OLQso
The most extreme cases of variability of cell position in the head are seen around the anterior bulb of the pharynx which fits fairly tightly in the body cavity and excludes these cell bodies from its region of maximum diameter. This leads to variability in the position of cell bodies with respect to the bulb. For example, in the N2U animal, OLQsoDL lies anterior to the bulb, whereas its symmetrical partner, OLQsoDR, lies posterior to the bulb (White et al., 1986).
Most neurons are born close to their ultimate positions and need migrate only short distances. However, there are a few neurons that must migrate long distances after they are born (NeuroFIG 4A,B) (Hedgecock et al., 1987 Montell, 1999). This group includes canal-associated neurons (CAN), which move from the anterior end to a location midway along the body HSN neurons, which move from the posterior end to close to the vulva and anterior lateral microtubule (ALM) neurons, which move posteriorly from the anterior edge of the intestine to midway within the anterior body. QR and QL neuroblasts also migrate extensively (NeuroFIG 4). QR and QL are born about 1 hour before hatching at symmetric locations on the right and left sides of the posterior body, respectively, but after cell migrations their terminally differentiated progeny reside in nonsymmetric positions. Soon after hatching, QR migrates anteriorly, whereas QL migrates posteriorly. Their descendents continue migrating asymmetrically to anterior positions on the right side and posterior positions on the left (Salser and Kenyon, 1992). Each Q lineage produces a mechanosensory neuron (AVM/PVM), a sensory neuron (AQR/PQR), an interneuron (SDQR/L), and two programmed cell deaths.
Some neurons display delayed maturation during development. The Y cell functions as a rectal epithelial cell until early larval stages, but later becomes terminally differentiated as PDA in the hermaphrodite. The embryonically born HSN neurons develop synapses onto newly born sex muscles only in the L3 and L4 stages (White et al., 1986). Similarly, VC neurons branch onto sex muscles in the L4 stage. DD motor neurons acquire their final synaptic connection pattern at the late-L1 stage, after the birth of VD neurons, and AVM neurons become connected to the anterior touch circuit at the late-L4 stage (Chalfie and White, 1988 Walthall et al., 1993).
2.1.2 Process Outgrowth, Establishment of Process Tracts and Guidance at the Midline
The nervous system of C. elegans displays handedness at many places. First, although the majority of neurons are in pairs and localize on the right and left sides of the animal in a bilaterally symmetric manner, there are many unilaterally placed single neurons. Additionally, members of some neuron pairs, such as SDQL/SDQR and AQR/PQR, are positioned far away from one another in a nonsymmetrical manner (NeuroFIG 4). Second, the two major cords of the animal, the VNC and dorsal cord (DC), are asymmetrical in their composition or location (NeuroFIG 4 and NeuroFIG 5). The DC is located at the left side of the dorsal hypodermal ridge, whereas the VNC has a thick fascicle on the right side of the ventral hypodermal ridge and a thin fascicle on the left. Third, the neurons in the body choose the side of the body on which to send their processes although the pair of HSN neurons extends its neurites ipsilaterally along the two VNC tracts, many neuron pairs, such as PVD and PDE, have both of their neurites in the right tract, which requires the left-sided process to cross the midline. Similarly, the VNC motor neurons, which are localized at the midline, make &ldquochoices&rdquo regarding the side on which to grow their circumferential processes, whereas all of them extend their ventral processes along the right VNC tract. The right fascicle of the VNC is further populated by some NR processes that exit the NR on the left side, but then decussate to the right to continue extending within the VNC (NeuroFIG 5, top panel right side and panel C) (White et al., 1986).
Asymmetry within the C. elegans VNC is established embryonically by pioneer neurons and midline cues provided by neuronal and nonneuronal (e.g., hypodermal and glial) tissues (NeuroFIG 4). AVG and PVT neurons mark the anterior and posterior boundaries of the VNC. AVG is the anterior guidepost neuron that pioneers the right tract of the VNC, whereas PVPR pioneers the left tract from the posterior, followed by the PVQL process (Durbin, 1987 Wadsworth and Hedgecock, 1996 Wadsworth et al., 1996). PVQ axons pioneer the lumber commissures and continue to travel alongside the PVP processes in the VNC. Although the PVPR axon is absolutely required for proper outgrowth of left-tract neurites, the AVG axon is essential for the correct outgrowth of only a subset of processes into the right tract (Hutter, 2003 Hutter et al., 2005). PVT, a single neuron in the preanal ganglion, serves as a guidepost neuron to growing axons from the lumbar ganglia in the posterior of the VNC. When PVT is ablated embryonically, these axons follow multiple routes to enter the VNC instead of making tight bundles in the two lumbar commissures (Wadsworth et al., 1996 Antebi et al., 1997 Ren et al., 1999). PVT is also required for maintenance of neurite architecture in the VNC post-embryonically, because in the absence of PVT, embryonically generated neurites are unable to maintain their positioning along the cord at the L1 stage and erroneously cross over the midline into the opposite fascicle (Aurelio et al., 2002 Hobert and Bülow, 2003). BDU processes are required for correct positioning of AVM branches in the NR (Chalfie and White, 1988). Notably, RIF neurons, which are the first processes to cross the ventral midline between the NR and the beginning of the VNC, are not essential for providing the pathway for guiding processes into the right VNC fascicle at the anterior decussation (Durbin, 1987 Hutter, 2003). The two neuron pairs, which decussate shortly after RIF, SABVs, and RIGs, are also not essential for this function.
Of the 302 neurons in the adult hermaphrodite,180 project axons/processes into the NR. In the developing embryo, these axons that form the nerve ring must navigate to the NR within commissural and longitudinal nerve bundles, recognize the region of the NR, make L/R side choices to enter the NR, make specific contacts with each other to form synapses and maintain these contacts during later growth. Additionally, head and neck muscle development has to be coordinated with the longitudinal and commissural tract and nerve ring development. Currently, little is known about the procession and control of the NR development. Based on studies of embryos at 350 min and 430 min (after first cleavage,) it has been suggested that SIBD neurons act as pioneers to might provide a substrate for the formation of early amphid commissure, while RIH and RMEV might help navigate the first axons entering the NR from the ventral side (Norris, C., Hall, D. H., Hedgecock, E. unpublished observations) (NeuroFIG 15-2). In the early neurula, head muscle cells directly surround the pharynx where the NR will form and hence may restrict the access of lateral axons to reach the NR until the muscle cells move dorsally and ventrally to the periphery to their usual positions next to the hypodermis. As they migrate, they are suggested to leave railing processes behind attached to the NR, forming the arms of the head muscles (see Somatic Muscle).
Outgrowth, branching, and shaping of neuronal processes, which are dependent on intrinsic cytoskeletal dynamics and extrinsic cues, are highly stereotyped in C. elegans. Mutant studies have uncovered several genes that seem to be involved in proper process outgrowth and suppression of excess axon branching (Altun-Gultekin et al., 2001 Knobel et al., 2001 Bülow et al., 2002). Neurons that extend commissures use the classical UNC-6/netrin and SLT-1/slit pathways, which act redundantly, as well as additional pathways that act in parallel to these, for circumferential guidance along the dorsoventral axis (for review, see Chisholm and Jin, 2005). Intrinsically, cytoskeletal rearrangements are regulated by Rac GTPases and the actin-binding protein UNC-115 (Yang and Lundquist, 2005). Extracellularly, guidance cues are modified by heparan sulfate proteoglycans, which affect neurite branching and patterning in a cellular context-dependent manner (Bülow and Hobert, 2006.) Although the mechanisms for branch-point control are still unclear, branching generally occurs under four circumstances: (1) Processes may enter midway along an existing nerve and bifurcate and grow in both directions (2) processes are confronted with two equivalent neighborhoods, such as the entrance to the NR, and they may split and grow into both (3) within the NR, processes may also bifurcate to enter two different neighborhoods and finally, (4) processes in longitudinal nerves may bifurcate and grow a branch circumferentially into another nerve (Hedgecock et al., 1987).
2.1.3 Developmental Plasticity
The C. elegans nervous system exhibits various forms of plasticity as it matures. At the end of the L1 stage, post-embryonically born body wall muscles and five classes of newly born motor neurons are incorporated into the existing motor system and novel neuromuscular junctions are established, suggesting reciprocal responsiveness between the muscles and motor neurons. The end of the first larval stage also marks the rewiring of the synaptic contacts of DD motor neurons after the birth of VD motor neurons. This rewiring is intrinsically controlled and is not dependent on VD, VA, or VB neurons (White et al., 1978). Additionally, the neurons maintain similar densities of synapses during the fivefold increase in body length as the animal goes through four larval stages, suggesting that the nervous system maintains a certain level of plasticity throughout life and adjusts itself to the overall growth.
2.2 Neuron Categories
C. elegans neurons fall into four functional categories defined by their circuitry: (1) motor neurons, which make synaptic contacts onto muscle cells (2) sensory neurons, which have obvious sensory specializations (behavioral or mutant paradigms now demonstrate defined sensory functions for most of these cells, but some cells only have inferred or yet obscure sensory capabilities NeuroTABLE 1) (3) interneurons, which receive incoming synapses from and send outgoing synapses onto other neurons and (4) polymodal neurons, which perform more than one of these functional modalities. A pair of pharyngeal neurons, NSML/R, have prominent secretory terminals and are classified as neurosecretory neurons (they also have motor function see Alimentary System - Pharynx). Besides these categories, there is a small subset of neurons whose functions are yet unknown. Some of these may be more important in process guidance or maintenance than in circuitry (Durbin, 1987 Chen et al., 2006 Hall et al., 2006).
The locomotory behavior repertory of C. elegans includes "crawling" on solid surfaces and "swimming/thrashing" in liquid media. A total of 113 of the 302 C. elegans neurons belong to the motor neuron category, and they control crawling and swimming behaviors as well as the motility of the alimentary and reproductive systems. Of these 113, 75 innervate 79 body wall muscles posterior to the head (16 neck and 63 body muscles) and belong to eight distinct classes (AS, DA, DB, DD, VA, VB, VC, and VD) (NeuroFIG 6, NeuroFIG 7 and NeuroFIG 8). A- and B-type motor neurons (VA, VB, DA, DB, AS) are cholinergic and stimulatory. D-type motor neurons (VD, DD) secrete &gamma-aminobutyric acid (are GABAergic) and are inhibitory and strictly post-synaptic to other motor neurons. VC motor neurons express several transmitters and their primary targets are vulval muscles. VA, VB, VC, and VD classes innervate ventral muscles, whereas DA, DB, DD, and AS classes innervate the dorsal muscles by sending commissures to the dorsal side (White et al., 1976, 1986).
The VNC neurons regulate the characteristic undulatory movement of the animal, which involves alternate contraction of the dorsal and ventral longitudinal muscle rows. These motor neurons synapse onto either both dorsal or both ventral muscle quadrants, thereby restricting the body&rsquos flexures to the dorsoventral plane, creating sinusoidal waves as the animal lies on its lateral side on the substrate. When the dorsal muscles are activated, the ventral muscles are reciprocally inhibited and vice versa. Bending against the substrate results in forward locomotion as a result of propagation of sequential contraction and relaxation waves passing backward along the body. D-type motor neurons have processes that are post-synaptic corecipients at the dyadic NMJs of stimulatory (A- or B-type) motor neurons, and the ventral D and dorsal D neurons work as reciprocal cross-inhibitors. Their GABAergic synaptic outputs are onto diametrically opposite muscles, so that when a ventral or dorsal muscle group is activated by a cholinergic motor neuron, the opposite group of muscles is inhibited and relaxed (NeuroFIG 6) (White et al., 1978 McIntire et al., 1993). D-type motor neurons are most important for resetting the animal&rsquos posture, for example, when reversing direction or initiating rapid movement (Jorgensen and Nonet, 1995 Jorgensen, 2006). In response to a touch, an animal that lacks GABA input shrinks due to unopposed contraction of both dorsal and ventral muscles. Once an animal gets moving, GABA input does not interfere with wave propagation however, it does affect the amplitude of the body waves.
Movement in either forward or reverse directions is regulated by signals from specific classes of command interneurons (NeuroFIG 6A). Forward motion is promoted by input from AVB and PVC interneurons onto DB and VB neurons, whereas backward motion is promoted by input from AVA, AVD, and AVE interneurons onto DA and VA neurons (NeuroFIG 6) (Chalfie and White, 1988 Driscoll and Kaplan, 1997 Von Stetina et al., 2006). Synaptic innervation of motor neurons by command interneurons occurs throughout the length of the VNC. Command interneurons establish the direction of locomotion, but are not thought to be involved in wave propagation down the length of the animal (Jorgensen and Nonet, 1995). It is currently unclear which neurons are involved in wave propagation, although proprioceptive inputs are thought to have a role. The command interneurons are not equivalent because ablation of AVA or AVB produces uncoordinated animals (after a bout of forward or backward motion, animals kink while trying to reverse their direction) that are touch responsive, whereas ablation of PVC or AVD mainly abolishes the touch-mediated locomotory responses, but does not result in any change in spontaneous locomotion (Chalfie et al. 1985).
The members of each class of body motor neurons are evenly distributed along the length of the ventral cord between the retrovesicular ganglion (RVG) and preanal ganglion (PAG). They create a longitudinal, synaptic fate map onto the body muscles (NeuroFIG 6C, NeuroFIG 7 and NeuroFIG 8). Within each class of motor neurons there is little or no overlap in the output regions of adjacent members (White et al., 1976). The cell bodies of motor neurons are covered by the hypodermal basal lamina and lie on top of the ventral hypodermal ridge or are wedged between the ridge and the processes of the right tract of the VNC.
Motor neurons are generated at two distinct developmental stages: first, around midembryogenesis and then, during the first larval stage (Sulston and Horvitz, 1977 Sulston et al., 1983). DA, DB, and DD are the only classes of motor neuron present in the VNC at hatching. They are born at midembryogenesis and simultaneously extend commissures to the DC. Command interneurons that make synapses onto them enter the VNC after motor neuron outgrowth is completed. During the L1 stage, DA and DB innervate dorsal muscles and DD innervates ventral muscles. DD dendrites receive input from DA and DB at dyadic synapses onto the dorsal muscle arms. After hatching, the other five classes (additional 56 motor neurons) are generated by 13 (W and Pn) blast cells (see Epithelial System - Hypodermis ). The anterior daughters of the first division of P cells (Pna) give rise to 53 of these (Sulston et al., 1983). The processes from these later-born cells insert themselves into the cord between existing fibers to establish contacts with appropriate command interneurons and muscle cells. After post-embryonic motor neurons are born, DD neurons reverse their synaptic polarity without undergoing any structural change in process placement (White et al., 1978). They rearrange their synaptic machinery to receive input from the nascent VA and VB motor neurons and send output to dorsal muscles. An additional excitatory class of neurons, SABVL/VR/D, innervates anterior ventral body muscles only in the L1 stage after this stage, they function as interneurons.
Unlike the body, the head of the animal is capable of making lateral movements as well as dorsoventral flexures, especially during foraging behavior. Head and neck muscles are innervated by about 11 classes of motor neurons in the NR in a complex pattern (see Somatic Muscle). Additional nerve&ndashmuscle contacts occur along the length of the sublateral cords (J. Duerr et al., unpubl.). Most axons in these nerve cords show periodic swellings filled with synaptic vesicles and sometimes have small presynaptic densities. The post-synaptic targets of these synaptic release zones are possibly the body muscles. The specialized motor neurons of the alimentary and reproductive systems that are associated with defecation and egg-laying muscles are discussed the Alimentary System - Rectum and Anus and Reproductive System - Egg-laying apparatus sections, respectively.
2.4 Sensory Neurons
C. elegans explores its environment and moves to favorable surroundings by chemotaxis, thermotaxis, and aerotaxis and escapes from harmful and noxious stimuli by avoidance/escape behaviors. The perception of environmental cues, including mechanical stimuli, temperature, many water-soluble and volatile chemicals, noxious substances, ambient osmolarity, oxygen levels, pH, and light, is accomplished through 24 sensillar organs and various isolated sensory neurons (NeuroTABLE 1) (Bargmann, 2006 Bergamasco and Bazzicalupo, 2006). Sensillar neurons perform most of the sensory functions. However, some sensory functions, including oxygen sensation and mechanosensation, are performed by nonsensillar neurons. Each sensillum contains ciliated endings of one or more neurons and often two types of glia: the socket cells and the sheath cells. Except for posterior deirids and phasmids, all sensilla are located in the head (see Neuronal Support Cells and Introduction IntroTABLE 1).
Through the function of these neurons, C. elegans navigates thermal, chemical, and oxygen gradients by modulating the probability of its turning behavior and speed of movement on a solid surface. Turning can be produced either by a reversal of movement followed by resumption of forward movement in a new direction or by omega turns in which the animals curl their whole body so that their heads get close to or even touch their tails before starting to move forward (NeuroFIG 6) (Pierce-Shimomura et al., 1999). Alternatively, the animal can accelerate its forward-directed movement after receiving a sensory signal.
Mechanical stimuli, including gentle touch along the body (e.g., with a soft hair), gentle touch to the nose, harsh touch along the body (e.g., with a wire), and tapping of the culture plate, are perceived through touch receptors and proprioceptors that fall into three classes according to their cytoskeletal specialization: (1) mechanoceptors with ciliated sensory endings (2) touch receptor neurons containing large-diameter, 15-protofilament microtubules (also called MT cells) and (3) neurons with processes containing synapse-free stretches and undifferentiated cytoskeletons (NeuroTABLE 1) (Herman, 1995 Driscoll and Kaplan, 1997 Syntichaki and Tavernarakis, 2004 Goodman, 2006 O&rsquoHagan and Chalfie, 2006). Mechanociliary neurons display features important for sensing any mechanical deflections over the worm&rsquos surface IL1, CEP, OLL, OLQ, ADE, and PDE cilia terminate embedded within the cuticle, and all of them except for IL1 are anchored in this cuticle by small electron-dense nubbins. Additionally, the distal sections of ADE, PDE, OLL, and CEP cilia contain an amorphous, dark, microtubule-associated material (TAM) that is also found in mechanocilia of other species. IL1 cilia contain a dark-membrane-attached disc at their tips. All mechanosensory stimuli lead to avoidance responses in the hermaphrodite.
Mechanosensory neurons detect force through mechanically-gated ion channels which produce touch- or stretch-evoked currents. These channels are generally formed by two protein superfamilies the TRP channels which are nonspecific cation channels composed of subunits with six transmembrane &alpha helices, and heterotrimeric DEG/ENaC channels which are permeable to sodium and sometimes to calcium (Arnadottir and Chalfie, 2010 Bounoutas and Chalfie, 2007 Kahn-Kirby and Bargmann, 2006). The C. elegans genome encodes 28 predicted DEG/ENaC proteins and 23 predicted TRP proteins(Goodman & Schwarz, 2003).
Gentle (low threshold) body touch.A gentle stroke of the animal&rsquos body with an eyelash is sensed by six touch receptor neurons (NeuroFIG 9 and NeuroFIG 10). The touch-response circuit additionally involves 6 interneurons and 69 motor neurons (Chalfie et al., 1985 Goodman, 2006). The processes of touch receptor neurons act both as dendrites receiving the touch stimulus and as axons carrying the signal to downstream neurons. If the animals are touched on the posterior half of the body, they either initiate or accelerate forward motion. If the stimulus is applied on the anterior half of the body, animals reverse and move backward. These two sensory fields (anterior and posterior) are defined by the arrangement of the touch receptor processes along the body axis. The ALM (anterior lateral MT cell) pair and AVM (anterior ventral MT cell) respond to stimuli applied on the anterior half, whereas the PLM (posterior lateral MT cell) pair sense those applied on the posterior half. The PVM (posterior ventral MT cell) is suggested to contribute to the response, although it cannot initiate a discernible touch response by itself. Animals that lack touch receptor neurons do not respond to light touch but are still capable of sensing harsh body touch (Chalfie and Sulston, 1981).
ALM and PLM cells are born during embryogenesis. ALM cells migrate posteriorly, a process that is completed before the elongation stage of the embryo (Sulston et al., 1983 Chalfie, 1993). In newly hatched larvae, the processes of these touch cells are located between the lateral hypodermis and the adjacent muscle quadrant. At about 12 hours post-hatching, they become engulfed by the adjacent hypodermis (Chalfie, 1993). Two other touch receptor neurons, AVM and PVM, are born post-embryonically about 9 hours after hatching at 20°C. Their processes run anteriorly within the VNC at its extreme ventral edge (NeuroFIG 5).
Each touch neuron process is 400&ndash500 &mum long in the adult and is filled with large-diameter (30 nm), 10- to 20-&mum-long, 15-protofilament MTs that overlap and bundle together through cross-links (Chalfie and Thomson, 1979, 1982). The tubulin dimers MEC-12 (&alpha-tubulin) and MEC-7 (&beta-tubulin) coassemble into these 15-protofilament structures (Fukushige et al., 1999). At hatching, ALM and PLM cells contain fewer and shorter MTs. By 12 hours, MTs start to increase in number and length and, by 36&ndash48 hours, adult levels are reached (Chalfie and Thomson, 1979, 1982).
The touch receptor neurons also transduce the plate-tap response, which is considered to involve a nonlocalized touch stimulus. In the tap response, signals from the anterior touch circuit (the producer of backward movement) tend to override those from the posterior one, causing animals to reverse direction or move backward in response to a tap to the culture plate. This preference becomes especially strong at L4&ndashadult transition (approximately 46&ndash51 hours post-hatching) when the late-developing AVM becomes connected to the anterior touch circuit by forming an inhibitory connection to the AVB interneurons (Chalfie and Sulston, 1981 Walthall and Chalfie, 1988 Chiba and Rankin, 1990).
Touch sensation modifies other behaviors of the animal for example, gentle body touch regulates pharyngeal pumping and egg-laying and resets the defecation cycle. These responses may be elicited by the synapses between the touch neurons and CEPs, deirid neurons, HSN motor neurons, and RIP interneurons (Syntichaki and Tavernarakis, 2004).
Harsh (high threshold) body touch.In the absence of all touch receptor neurons, the animal still retains the ability to respond to harsh touch along the body (e.g., with a wire), and this response can be eliminated by killing the PVD cells (recent results suggest ALM neurons also sense harsh touch (Chatzigeorgiou et al., 2010)). Hence, PVD neurons, which are presynaptic to command interneurons AVA and PVC, are proposed to be the mechanoceptors for harsh body touch (Way and Chalfie, 1989). In adult animals, PVD neurons show extensive branching along the body wall, from the tail to the neck of the animal, covering dorsal and ventral territories (NeuroFIG 3 and NeuroFIG 10) (Halevi et al., 2002). Multiple short branches arise from the main branches at the level of the muscle quadrants and these branches give rise to further branches subventrally and subdorsally. The molecules needed for mechanotransduction of harsh touch are not well known (O&rsquoHagan and Chalfie, 2006). mec-3 mutant animals, in which PVD neurons do not differentiate properly, retain the ability to respond to harsh touch to the head and tail (Way and Chalfie, 1989 Tsalik et al., 2003 O&rsquoHagan and Chalfie, 2006). A harsh touch defect in the tail is seen in the absence of PVC neurons, which may be sensing the stimulus directly or indirectly through other neurons (NeuroFIG 10C).
Harsh (high threshold) head/nose touch.Three classes of neurons, FLP, ASH, and OLQ, form ciliated endings in the nose, which transduce head-on nose touch stimuli that results in reversal of movement (NeuroFIG 10) (Kaplan and Horvitz, 1993). FLP neurons have a similar branching pattern to PVDs in the head (topologically they complement where PVD branches end in the neck, FLP branches start) and act together with ASH neurons to sense harsh mechanical stimuli to the head (Albeg et al., 2011 Chatzigeorgiou and Schafer, 2011). OLQs may enhance this mechanoreception (NeuroFIG 10A). ASH and FLP neurons are coupled to the locomotion circuitry via gap junctions and chemical synapses made onto AVA, AVB, and AVD interneurons.
Gentle (low threshold) nose touch.Two classes of neurons, OLQ and IL1, function in aversive head-withdrawal reflex and suppression of lateral foraging movements of the head in response to gentle touch on the ventral or dorsal tip of the nose (Hart et al., 1995). IL1 and OLQ synapse onto NR motor neurons, and IL1 makes direct synapses onto head muscles. OLQ may also function in mechanosensory feedback for foraging, as the rate and amplitude of foraging in unstimulated animals is affected in OLQ-ablated animals. FLP neurons also respond to gentle nose touch and activate an escape behavior (Chatzigeorgiou and Schafer, 2011). OLQ and CEP neurons indirectly facilitate gentle nose touch responses in the FLP head nociceptors via the RIH interneuron which acts as the integrating neuron of this circuit hub(Chatzigeorgiou and Schafer, 2011).
Texture sensation.C. elegans can sense mechanical attributes of the surface material on which it navigates through the function of dopaminergic CEP, ADE, and PDE neurons (NeuroFIG 10) (Sawin et al., 2000). The capability to distinguish texture (e.g., small, round objects) helps animals to detect food in their environment, in addition to olfactory cues, and causes slowing of locomotion (food-induced slowing response).
Proprioception.Worms may sense changes in stretch and tension within their own bodies, especially during locomotion. Some neuron processes with morphologically nonspecialized, synapse-free, bare-wire portions are thought to transduce proprioceptive stimuli. Such properties have been hypothesized for many neurons, including the A- and B-type motor neurons, PHC, some pharyngeal neurons, and male tail neurons (NeuroFIG 6) (Hall, 1977 Sulston et al., 1980 Albertson and Thomson, 1984 Hall and Russell, 1991 R. Lints and D.H. Hall, unpubl.). Some of these may function to sense the degree of bending during undulatory movement, providing sensory feedback about the worm&rsquos body posture and coordinating the degree and timing of alternating contractions and relaxations of muscles (White et al., 1986 Tavernarakis et al., 1997). A similar proprioceptive property has been proven for the DVA neuron, in which stretch sensitivity is transduced by the trp-4 membrane channel (Li et al., 2006). The DVA axon travels from its cell body in the tail anteriorly to the NR via the VNC, but it is not known to show any specializations by TEM that mark its stretch-sensitive portion. PVD may have a role in proprioception, as ablation of PVD leads to defective posture (Albeg et al., 2011). PVD and DVA neurons are presynaptic to both forward and backing command interneurons and provide input to both anterior and posterior touch circuits to maintain overall activity of the circuits. Animals lacking these neurons respond to tap stimulus with diminished forward accelerations and reversals, and mutation of the trp-4 channel or laser ablation of DVA gives rise to animals with body bending defects (Wicks et al., 1996 Driscoll and Kaplan, 1997 Li et al., 2006).
Body wall muscles may also sense the degree of stretch within them and modulate the contractions required for organized locomotion (Liu et al., 1996). Putative &ldquoproprioceptive&rdquo endings in the pharynx are fastened by AJs or hemi-AJs to the pharyngeal cuticle (I1, I2, I3, I6), pharyngeal muscle specializations near the lumen (M3, NSM), or a muscle cell soma (I5) (Albertson and Thomson, 1976). Physiological experiments support that a few of these pharyngeal neurons may be stretch sensitive (Avery and Thomas, 1997).
Nociception is the ability to recognize toxic and harmful components in the environment that allows for avoidance and survival. For C. elegans, aversive cues include mechanical stimuli (both light and harsh touch), certain odorants and toxic chemicals, high osmotic strength, acidic pH, extremes of heat and cold (see thermonociception below), and certain light wavelengths (Culotti and Russell, 1978 Tobin and Bargmann, 2004). Many of the chemicals that are noxious for C. elegans are toxic or bitter for other animals as well, including sodium dodecyl sulfate (SDS), quinine, and heavy metals such as copper (Sambongi et al., 1999 Tobin and Bargmann, 2004). It should be noted that animals in diapause are much more stress-tolerant, including heat-shock conditions (Wittenburg and Baumeister, 1999, see Dauer chapter). ASH neurons are polymodal nociceptors that detect nose touch, high osmotic strength (high concentration of salts or sugars), acidic pH, quinine and other bitter compounds, heavy metals, and aversive odors such as 2octanone, octanol, and benzaldehyde (NeuroTABLE 1). ASH neurons have cilia exposed to the outside and generate a rapid escape response in the form of reversal and turning upon encountering noxious stimuli (NeuroFIG 6) ( et al., 1986 Troemel et al., 1997 Hart et al., 1999). All ASH-mediated sensory behaviors require the TRPV channels OSM-9 and OCR-2 (Tobin et al., 2002). The diverse array of nociceptive cues sensed by ASH neurons generate distinct amplitudes and patterns of glutamate release from these neurons onto the target command interneurons that allow separable behavioral responses (Mellem et al., 2002).
2.4.3 Chemosensation and Odorsensation
C. elegans can detect and discriminate a wide range of chemical compounds, including water-soluble chemicals (chemosensation or gustatory sensation) such as anions, cations, cyclic nucleotides, biotin, and amino acids and volatile chemicals (odorsensation or olfactory sensation) such as alcohols, aldehydes, ketones, esters, pyrazines, thiazoles, and aromatic compounds (Bargmann and Mori, 1997 Mori, 1999 Bargmann, 2006). There are 32 chemo/odorsensory neurons that fall into 14 classes. Of these, 22 are paired neurons of the amphid sensilla, four are paired neurons of the phasmid sensilla, and six are IL2 neurons of the inner labial sensilla (NeuroTABLE 1 see Neuronal Support Cells). Most of the individual amphid neurons detect either water-soluble or volatile chemicals and direct either attraction or aversion, although lower concentrations of certain chemicals may be sensed as attractive, whereas higher concentrations may become repellent. A few neurons may sense both attractive and aversive cues (NeuroTABLE 1) (Bargmann and Horvitz, 1991 Bargmann et al., 1993 Troemel et al., 1997).
The ADF, ASE, ASG, ASI, ASJ, and ASK neurons mediate chemotaxis to water-soluble attractants. Among these, ASE seems to be the main sensor, with others having weaker roles. ASE is also unique because the two ASE neurons have distinct functions the ASER preferentially detects chloride and potassium ions, whereas the ASEL preferentially senses sodium ions (Pierce-Shimomura et al., 2001). ASH neurons are the main nociceptors and mediate avoidance from water-soluble and volatile cues. ASH is complemented by other amphid neurons in these functions ADL neurons contribute to osmosensation and avoidance from octanol, copper, and cadmium, whereas ASK and ASE contribute to avoidance of SDS and to cadmium and copper, respectively (Sambongi et al., 1999 Hilliard et al., 2002). ASJ neurons participate in formation and recovery by detecting dauer-inducing (dauer pheromone) and dauer-suppressing (food) signals in different developmental stages. ADF, ASI, and ASG function to inhibit dauer formation under favorable conditions (Bargmann and Horvitz, 1991). The three &ldquowing&rdquo cells AWA, AWB, and AWC sense volatile chemicals, and each neuron is preferentially linked to a particular behavioral response (Wes and Bargmann, 2001). Whereas AWC and AWA mediate odortaxis to volatile attractants, AWB detects aversive odorants important for long-range escape behavior.
As described above, C. elegans lies on either of its sides and moves either forward or backward using a sinusoidal-like undulation by alternately contracting its body wall muscles along the ventral and dorsal surface. Most of the time, the animals simply move forward (smooth runs), but this forward locomotion is occasionally interrupted by a number of processes such as omega-turns, pirouettes and gentle turning. During an omega-turn the worm makes a deep bend with the worm&rsquos head often contacting its tail, before the animal returns to forward motion along a new heading. Pirouettes are a series of reversals with one or more omega-turns that allow the worm to make major re-orientations in its direction of movement. Gentle turns (steering) are generated when the worm gradually changes its heading by a biased head swing during forward locomotion. Pirouettes appear to occur randomly, while steering appears to be a more directional process. Chemotaxis is driven by gently steering up the gradient as the worm moves forward and by altering the probability of pirouette initiation by which runs toward lower concentration are interrupted, whereas runs toward the attractant are sustained, eventually biasing the locomotion toward the higher concentration of the chemical (Appelby, 2012 Pierce-Shimomura et al., 1999 Iino and Yoshida, 2009).
As a cold-blooded soil nematode, C. elegans can tolerate a limited temperature range (
12-27°C) at which it is both fertile and viable (Hedgecock and Russell, 1975). C. elegans can accurately detect temperatures within this range, and this is reflected in its thermotactic behavior. Following cultivation with food at temperatures ranging from 15°C to 25°C, it migrates to the cultivation temperature on a temperature gradient and continues to move isothermally at that temperature. In contrast, the animals disperse away from the temperature at which they were previously starved (Hedgecock and Russell, 1975 Mori, 1999). This thermal preference/avoidance behavior is plastic and can be reset to a new temperature associated with presence/absence of food within 2&ndash4 hours of cultivation at that temperature. Through thermotactic behavior, C. elegans can escape unfavorable environments and regulate its position in the upper levels of soil, which may display large vertical and temporal temperature gradients. Behaviorally, C. elegans migrates towards its preferred temperature by modulating its turning rate and run length as a function of temperature change. Once it reaches within 3°C of its preferred temperature, it can fine-tune its tracking to 0.05°C differences by constantly reorienting its head movement (Ryu and Samuel, 2002 de Bono and Maricq, 2005)
There are three thermosensors in C. elegans the amphid AFD neurons (also called &ldquofinger&rdquo cells) are the major thermosensors (NeuroTABLE 1 see Neuronal Supportal Cells), while the amphid AWC and ASI neurons are supportive (Mori and Ohshima, 1995 Kuhara et al, 2008 Ohnishi et al, 2011 Beverly et al, 2011). AFD neurons have complex, brushlike structures at their dendritic ends that are completely embedded in the amphid sheath. Animals in which AFDs are killed are athermotactic. TAX-6 (calcineurin), three receptor-type guanylyl cyclases which function redundantly (GCY-8, GCY-18, and GCY-23), and cGMP-dependent TAX-2/TAX-4 cation channel have been shown to be involved in thermosensation in AFD (Kuhara et al., 2002 Inada et al., 2006). When tax-6 is mutated, animals display a thermophilic phenotype, whereas gcy-23, gcy-8, and gcy-18 triple mutants show a cryophilic or athermotactic phenotype. In AWC, heterotrimeric G-protein signaling and cGMP-dependent TAX-4 cation channel are involved. In the current model for thermosensation, the downstream AIY interneuron is bidirectionally regulated by AFD and AWC. Thermosensory information is transmitted from AFD and AWC to AIY through EAT-4/VGLUT-dependent glutamatergic neurotransmission. Glutamatergic signals from AFD inhibit AIY via activation of GLC3 (glutamate-gated chloride channel) and induce migration towards colder temperature. Glutamatergic signals from AWC, on the other hand, stimulate AIY to induce migration towards warmer temperature (Kuhara et al, 2008 Ohnishi et al, 2011). When AI Y are killed animals become cryophilic and migrate to colder temperatures than the cultivation temperatures, while ablation of AIZ neurons, which are the main postsynaptic target of AIY, makes animals thermophilic and induce them to migrate to warmer temperatures (Mori, 1999).
C. elegans also reacts to noxious (extreme cold or hot) temperatures. A prolonged exposure at 30°C results in an induction of the heat-shock response, and the animals become sterile within a few hours (Lithgow et al., 1995). Behaviorally, when they encounter a noxious heat source they respond with a reflexive withdrawal reaction (thermal avoidance response) (Liu et al., 2012 Wittenburg and Baumeister, 1999). PVD neurons in the body respond to acute cold shock, while AFD and FLP neurons in the head and PHC neurons in the tail sense noxious high temperatures (
35-38 o C)(Chatzigeorgiou et al., 2010). This nociceptive heat response utilizes a different neural circuit than thermotaxis and the response of C. elegans to noxious high heat is modulated by glutamate and by the neuropeptides encoded in the flp-1 locus. Two channel protein families contribute to thermonociception in C. elegans in distinct neurons: the TAX-2/TAX-4 cyclic nucleotide-gated channels and thermal-gated TRPV channels (TRPA, TRPM and TRPV ion channel families are considered "thermoTRPs" the gating of these channels by temperature is facilitated by chemical signals)(Hall & Treinin, 2011). Upon encountering noxious heat, TAX-2 and TAX-4 become activated in AFD neurons by cGMP which is mainly generated through the activity of GCY-12, but also to a lesser extent by GCY-8/18/23. In FLP and PHC neurons thermonociceptive signal transduction involves the OCR-2 and OSM-9 TRPV channels which can assemble into a heteromultimeric channel complex. PVD response to cold requires TRPA-1 channel (Chatzigeorgiou et al., 2010).
2.4.5 Light Sensation
Light stimuli induce a photophobic, movement-reversal response in C. elegans. Recently, it has been found that this response peaks in the high-energy ultraviolet (UV) range (blue-violet) and the head sensory neurons are apparently not required for this behavior (Burr, 1985 K. Miller, pers. comm.). It is suggested that the response originates in the VNC, although the exact sensory mechanism is yet to be described.
2.4.6 Oxygen and Carbon dioxide Sensation
C. elegans lacks a specialized respiratory system and uses diffusion for gas exchange. It can sustain a normal rate of metabolism between 2% and 21% ambient oxygen due to diffusion of oxygen to its tissues through the pseudocoelomic fluid, in which all tissues bathe (Van Voorhies and Ward, 2000). When cultivated under standard laboratory conditions, with a linear gradient from anoxia to atmospheric oxygen in the gas phase, C. elegans rapidly moves to an intermediate preferred oxygen concentration of between 7% and 14% oxygen, avoiding both high and low oxygen levels, although this response can be modified by environment and experience (Gray et al., 2004 Cheung et al., 2005 Rogers et al., 2006). In the wild, C. elegans lives close to decaying organic matter where it is exposed to an air/water interface with rapidly shifting oxygen tensions (0&ndash21%) due to consumption of oxygen by microbes. Ambient oxygen levels may, therefore, be perceived as indicating the presence of food by this animal. Oxygen sensation is performed by a distributed network of neurons that includes AQR, PQR, and URX, possibly gcy-35-expressing SDQ, ALN, and BDU, and osm-9-expressing (nociceptive) ADF and ASH neurons (White et al., 1986 Gray et al., 2004 Chang et al., 2006). AQR, PQR, and URX may perform a head-to-tail oxygen comparison achieved through their positions along the body in close contact with the pseudocoelom because they are suggested to function to monitor the pseudocoelomic fluid, including its oxygen content (NeuroFIG 11) (Rogers et al., 2006). AQR is a right-sided neuron, derived post-embryonically from the QR blast cell PQR is a left-sided neuron, derived post-embryonically from the QL blast cell. Both have ciliated endings. The AQR ending is free within the pseudocoleomic cavity, whereas the PQR ending lies close to the pseudocoelom, but is wrapped by the phasmid socket cell (see Neuronal Supportal Cells). URX cell bodies lie within the pseudocoelomic cavity. Similar to URX, AQR, and PQR neurons, SDQ, BDU, ALN, and PLN express soluble guanylate cyclases (sGC) that bind to molecular oxygen, consistent with a primary oxygen-sensing function for these AQR neurons. SDQs are also similar in lineage, morphology, and neural connectivity to the AQR and PQR neurons. Additionally, nociceptive ADF and ASH neurons may be modulatory or respond to oxygen directly. The output of the aerotaxis neuron network converges on AVA, the command interneuron responsible for generating backward motion and, hence, avoidance. The presence or absence of food modulates the basic aerotactic responses of hypoxia and hyperoxia avoidance. Modulation of hyperoxia avoidance is accomplished through the neuropeptide receptor NPR-1, the transforming growth factor-&beta (TGF-&beta)-related protein DAF-7, and serotonin production by the ADF neurons, whereas hypoxia avoidance seems to be mediated through a neuronal network that is independent of these pathways (Chang et al., 2006).
In the wild, C. elegans inhabits rotting material which contains a broad range of CO2 levels, however as in other animals, high CO2 levels are toxic causing deterioration of muscle organization, reducing fertility and slowing development above 9% (Bretscher et al., 2008 Hallem and Sternberg, 2008 Sharabi et al, 2009). Thus, the animal typically shows an acute avoidance response to CO2 (especially well-fed animals) when CO2 level is above 0.5%. Animals also respond to changes in ambient CO2 levels. Primary CO2 sensors are AFD, BAG and ASE neurons (Bretscher et al., 2011). The signal pathway for CO2 response in AFD and BAG include the TAX-2/TAX-4 cGMP-gated heteromeric channel and the atypical soluble guanylate cyclases that also mediate oxygen responses in BAG. AFD neurons respond to increasing CO2 by a fall and then rise in Ca 2+ and show a Ca 2+ spike when CO2 decreases. BAG and ASE are both activated by CO2 and remain tonically active while high CO2 persists. The CO2 responses in AFD, BAG and ASE neurons do not habituate upon multiple exposures to CO2. The modulators of the CO2 -response include physiological state of the worm, the neuropeptide Y receptor, NPR-1 , and calcineurin subunits, TAX-6 and CNB-1.
As in other organisms, interneurons comprise the largest group of neurons in the nematode. They function as information processors, receiving inputs from one or more classes of neurons and relaying outputs onto other neurons. They are suggested to compare and process sensory inputs in individual neuronal circuits and modulate the decision to execute a given motor program. They also function as circuit couplers where information from two or more circuits converge to establish circuit hierarchies. As an example, AVF, AVJ, and AVB interneurons link the neural networks for egg-laying and locomotion and function in temporal coordination of these two behaviors (Hardaker et al., 2001).
2.6 Polymodal Neurons
Some C. elegans neurons perform more than one type of circuit function, including both motor and sensory functions or interneuron&ndashmotor neuron or interneuron&ndashsensory neuron functions (White et al., 1986). Polymodal neurons are much more common in the male tail circuitry than anywhere else (Sulston et al., 1980 S.W. Emmons et al., unpubl.). M3 neurons of the pharynx have both motor and sensory functions. NSM neurons are both neurosecretory and motor neurons, and they may also have proprioceptive function (Albertson and Thomson, 1984). A- and B-type VNC motor neurons are suggested to be proprioceptive. IL1 neurons in the head perform mechanosensory, motor, and interneuron functions, whereas OLQ neurons are both mechanosensory and interneurons. RIM, SMB, SMD, RMD, RMH, and RMF classes of head neurons seem to be both motor and interneurons. AVL is a motor neuron with additional interneuron-type synapses. DVA is an interneuron that also functions as a stretch-sensitive sensory neuron. DVB is a motor neuron for enteric muscles and is also an interneuron. Alternatively, some neurons have multiple functions within one modality. ASH sensory neurons, for example, function as mechanosensory, osmosensory, odorsensory, and nociceptive, and ADLs are chemosensory, odorsensory and nociceptive.
Most neuron cell bodies in C. elegans are grouped into ganglia that are typical of invertebrates (Chitwood and Chitwood, 1950 White et al., 1986 Hall et al., 2006). C. elegans ganglia contain clusters of cells but few or no synapses. All except the anterior ganglion are bounded by the basal lamina of the hypodermis. The neuron processes extend from each of these ganglia, traveling in longitudinal nerve bundles into various regions of synaptic neuropil, where they form chemical and electrical synapses. The most prominent neuropil regions are the NR, VNC, and preanal ganglion. In addition to the ganglia, many neuron cell bodies lie in tandem along the length of the VNC. A few other neuron cell bodies lie singly or in small groups along the lateral body wall or within the pseudocoelom (URX, CEPD).
2.8 Process Bundles
Most neuron processes fasciculate into organized bundles (nerves or nerve cords) that may comprise as few as two or as many as 50 processes and run in parallel over long distances within the body (NeuroFIG 7 and NeuroFIG 8). Most of these processes run longitudinally along the body wall, except where they enter the NR. Most nerve cords are specialized to include limited functional groupings. For instance, the amphid nerves in the head and the phasmid nerves in the tail include only sensory dendrites and travel directly from sensory endings to related neuron cell bodies in local ganglia. Conversely, many neuron processes of the VNC, DC, and NR have mixed functions. The number and spatial arrangement of processes within the nerve tracts are essentially conserved between animals (White et al., 1976, 1983, 1986 Chalfie and White, 1988). Neighboring processes generally stay closely associated for long distances, and synapses are made en passant between adjacent processes. The neighborhoods, therefore, determine connectivity between neurons. Switching between neighborhoods, which most commonly occurs at the junctions of process bundles, increases the number of potential synaptic partners for a given neuron. The VNC is the major longitudinal nerve and splits posteriorly to the excretory pore into major (right side) and minor (left side) tracts that flank the ventral hypodermal ridge (NeuroFIG 5). In adult animals, the left VNC tract contains six processes and the right approximately 54 processes due to the decussation of the majority of fibers exiting the NR from the left side (Hedgecock et al., 1990). Near the junction of the NR, anterior to the decussation, the ventral ganglion region contains 170 processes. The VNC is continuous with the RVG at the anterior and with the PAG at the posterior end. Many of the tail neuron processes enter the right tract of the VNC, although a few enter the left tract.
In the VNC, motor neuron processes may navigate between different neighborhoods to accommodate input from interneurons within the fascicle as well as their output to muscle arms positioned outside of the cord. This switch in neighborhood generally occurs at the transition between the presynaptic and post-synaptic regions of each motor neuron. The second largest nerve in the nematode, the DC, is a single tract localized on the left side of the dorsal hypodermal ridge and mainly consists of commissural processes from the VNC motor neurons joined by the processes of a small set of neurons in the head (RMED, RID) and tail (PDA, PDB).
The processes within a nematode nerve cord are nonmyelinated, and available physiological evidence suggests that they do not conduct action potentials (Davis and Stretton, 1992 Goodman et al., 1998). All nerve bundles run in direct contact with the hypodermis, with which they share a common basal lamina separating them from the pseudocoelom or neighboring muscle tissue.
Commissures are circumferential tracts that are created by neuron processes passing from one longitudinal nerve to another through dorsoventral routes. Whereas in higher animals a commissure normally consists of dozens or even thousands of processes, in the nematode a commissure can consist of a single process that pioneers its own route along the body wall. The major commissures include amphid and deirid commissures in the head and lumbar, dorsorectal, and dorsolateral commissures in the tail. There are more than 40 individual commissures along the length of the body where VNC motor neuron processes extend to reach the dorsal side (NeuroFIG 7). The NR, which comprises the largest and most complex region of neuropil in the animal, is essentially an enlarged commissural region encircling the pharyngeal isthmus, with some 200 processes involved, most running a half-circle around the ring. Inside the pharynx, two shorter commissures, the pharyngeal nerve ring and the terminal bulb commissure, connect dorsal and sub-ventral pharyngeal nerve cords (see Alimentary System - Pharynx).
Topologically, the commissures follow two types of routes: medial and lateral (NeuroFIG 12) (White et al., 1986 Durbin, 1987). The fibers in the NR follow a medially positioned route between the basal face of the hypodermis and the central muscle arm plate. During development, pioneer axons for the NR are postulated to grow inwardly along extensions of the hypodermis or along the muscle arms of the head muscles, which themselves may be organized by the GLR scaffold cells (See GLR cells). Other commissures following such medial routes include those from the dorsorectal ganglion to the preanal ganglion in the tail (Hall, 1977 Hall and Russell, 1991) and the ventrally directed HSN processes.
Laterally positioned commissural routes are much more common. In these cases, neuron processes travel singly or in groups along a closely confined space underneath the body wall muscles, always in close apposition to the thin sheet of hypodermis that covers the muscle. Again, the nerves remain separated from the muscle by the basal laminae of the muscle and hypodermis. The right-sided VNC neuron commissures reach the DC by crossing over the dorsal hypodermal ridge.
2.9.1 Commissures in the Head
There are four major commissures in the head: right and left amphid commissures and right and left deirid commissures (NeuroFIG 13 and NeuroFIG 14). The amphid commissures on both sides are mainly composed of axons of the amphid neurons that extend from the neuron cell bodies toward the ventral nerve cord, passing between the ventral body wall muscle and a thin sheet of hypodermis (NeuroFIG 15 and NeuroFIG 16). They also contain processes that come from the ventral cord. Processes of two such neurons, SAAV and SABV, join the anterior ventral sublateral cords as they exit the amphid commissures.
Amphid commissures are located laterally to the junction of the pharyngeal isthmus and terminal bulb. The posterior sections of the amphid commissures are also referred to as sublateral commissures because they are composed of fibers of ventral sublateral cords. Of these, anteriorly traveling PLN processes dive through the amphid commissure to join the VC on their way to the NR, whereas posteriorly traveling SIBV, SMBV, SIAV, and SMDV processes use amphid commissures to join the ventral sublateral cords. The compositions of the right and left amphid commissures are nearly mirror images of each other. The RID process (on the left side) and the SABD process (on the right side) are the exceptions.
The deirid commissures run near the posterior part of the terminal bulb of the pharynx (NeuroFIG 16 and NeuroFIG 17). Originating from their neuronal cell somata on the lateral sides of the head, the processes within the deirid commissures first travel posteroventrally and then medially among the cells of the retrovesicular ganglia until they join the VC. They turn anteriorly in the VC and travel to the NR. AQR is present only on the right side.
There are three pairs of commissures in the tail: right and left lumbar commissures (also called ano-lumbar commissures), right and left dorsorectal commissures (also called rectal commissures), and right and left dorsolateral commissures (NeuroFIG 8 and NeuroFIG 18). The lumbar commissures are made of processes of PQR (left side), DA8 (left side), DA9 (right side), PDB (right side), PDA (right side), PVR (right side), PHAL/R, PHBL/R, PHCL/R, PVQL/R, LUAL/R, PVCL/R, PVWL/R, and PVNL/R. The majority of fibers in the lumbar commissures travel ventroanteriorly toward the PAG after originating from the lumbar ganglia neurons. However, the processes of PDA, DA9, DA8, and PDB neurons, which are situated in the PAG, travel posterodorsally through the lumbar commissures. The PDB process then continues traveling toward the tail and makes a dorsal turn within the tail tip to reach the DC, whereas the processes of PDA, DA9, and DA8 motor neurons continue their dorsal trajectory to the DC along the dorsolateral commissures. The dorsorectal commissures contain processes from DVA (right-side), AVFR (right-side), DVB (left-side), DVC (left-side), and AVG (left-side) neurons. The three dorsorectal ganglion neurons (DVA, DVB, DVC) grow their processes ventrally toward the PAG (Hall and Russell, 1991).
Of the 46 VNC motor neurons that extend processes to the dorsal side, 44 (7 DA, 7 DB, 6 DD, 13 VD, and 11 AS) send their processes via body commissures, whereas DA8 and DA9 send processes to the DC via tail commissures (NeuroFIG 7 and NeuroFIG 18). The commissural processes in the body are sandwiched between muscle and hypodermis as they travel along the lateral body wall. Most of these processes travel on the right side of the animal however, 11 of them (DA1, DA3&ndash7, DB2, DB4, DB5, DD1, VD2) make left-sided commissures (NeuroFIG 19 and NeuroFIG 20). Many travel alone or at times, two processes can join together to travel in a single commissure. The anteriormost right (made by VD1 and SABD processes) commissure is located near the posterior end of the terminal bulb of the pharynx, whereas the left (made by DB1) is around the procorpus of the pharynx (NeuroFIG 8 and NeuroFIG 20). The posteriormost body commissure (made by AS11) is close to the preanal ganglion in the tail. Along the body, other neuron processes travel dorsally or ventrally to reach longitudinal process tracts and make shorter commissures. These include SDQ dorsal processes extending to the dorsal sublateral tract on each side HSN, PLM, PDE, and PVD ventral processes to the VNC on each side AVM ventral process to the VNC on the right side and PVM ventral process to the VNC on the left side.
The most important concentrations of synapses (also referred to as neuropils) are the NR, VNC, and DC. The tail has an additional region of specialized neuropil in the preanal ganglion that is substantially enlarged in the adult male tail. Very sparse chemical synapses are also found along the sublateral nerve cords, but practically none are found in the other longitudinal nerves, including the amphid, phasmid, or the lateral nerves. Synapses involving commissural axons are apparently rare except for those locations in which a commissure crosses in close proximity to a longitudinal nerve. In general, the ganglia consist entirely of cell bodies and have no synapses. However, the lumbar and dorsorectal ganglia of the male tail also include small regions of neuropil. Occasional chemical synapses may also include alternate cell types as apparent post-synaptic partners, including hypodermal fingers in the nerve cords, marginal (epithelial) cells in the pharynx, the excretory gland, and some sex-specific epithelial cells.
2.10.1 Chemical Synapses
In C. elegans, chemical synapses may occur between one presynaptic and one post-synaptic cell (a monad) or more than one post-synaptic partner (a polyad two recipients make it a dyad and three recipients make it a triad), and one may be muscle (NeuroFIG 21). Chemical synapses are made en passant between neighboring processes where synaptic swellings are formed along the process shafts. These synapses are distinguished by the presence of a small (
50 nm wide and 100&ndash400 nm long), electron-dense presynaptic density on the cytoplasmic side of the membrane. A small cluster of synaptic vesicles lies near this density both docked and in reserve pools that comprise the &ldquoactive zone&rdquo (Weimer and Jorgensen, 2003 Rostaing et al., 2004 Zhen and Jin, 2004 Nakata et al., 2005). Further away from the active zone is a periactive zone, where molecules that coordinate synaptic organization and growth are localized and vesicle membrane may be recovered by endocytosis (Jin, 2002 Rostaing et al., 2004 Nakata et al., 2005). The size of the presynaptic region varies considerably even within the same neuron or among synapses of the same type of neuron (Jin, 2005).
Unlike vertebrates, little or no specialization is evident by standard TEM on post-synaptic membranes in C. elegans, and, therefore, proximity determines synaptic partners. Immunochemical staining has recently confirmed that post-synaptic receptors are clustered on the post-synaptic processes, very close to the presynaptic release zone, and improved fixation methods show the presence of small post-synaptic densities (NeuroFIG 21) (Gally et al., 2004 Jin, 2005 J.-L. Bessereau and R. Weimer, pers. comm.). Recent physiological studies of neuromuscular junctions in C. elegans support the observation that a single neuron can elicit responses in multiple post-synaptic elements (Liu et al., 2006). The synaptic cleft generally appears unspecialized in the nematode.
As in other organisms, rapid neurotransmission in C. elegans uses classical neurotransmitters, including various monoamines, acetylcholine, GABA, and glutamate. The synaptic vesicles (SV) for classical neurotransmitters that are present at the release zone tend to be small and spherical (30&ndash45 nm in diameter) and have clear contents. The absolute number of nearby vesicles ranges from 10 to 100 in the readily releasable pool. Docked vesicles are closely tethered to the presynaptic membrane within 75 nm of the presynaptic density. Cytoplasmic dense material often surrounds some or all of these vesicles, making the release zone darker than the nearby axoplasm. Vesicles are initially formed in the cell body and may lie in small clusters in the soma cytoplasm before being actively transported down the axon (Hall and Hedgecock, 1991). These transport vesicles are larger in diameter (50 nm) and more electron-dense in contents than the vesicles clustered at the release zone. While traveling along the axon as the cargo of MT-based motors, transport vesicles lie in close proximity to the MT bundle of the nerve process (Hall and Hedgecock, 1991 Zhou et al., 2001).
In contrast to SVs, which are clustered near the release sites, large dense-core vesicles (LDCV 40&ndash50 nm) that contain proneuropeptides and copackaged proprotein-processing enzymes are seen throughout the presynaptic compartment (NeuroFIG 21D) (Jacob and Kaplan, 2003). C. elegans contains more than 150 putative neuropeptides that are thought to modulate synaptic function but can also mediate rapid neurotransmission via gated ion channels (Richmond and Broadie, 2002). A large fraction of C. elegans neurons use peptide neurotransmitters, and a range of behavioral defects are observed in mutants lacking these enzymes. The molecular mechanisms used for transport and membrane fusion of LDCV share some components, such as UNC-104, with those used in rapid synaptic vesicle neurotransmission.
Small clusters of free ribosomes have been seen at both presynaptic swellings and in post-synaptic processes (Rolls et al., 2002). These ribosomes may permit local translation of messages in distal neurites.
2.10.2 Neuromuscular Junctions
Neuronal input to muscles occurs at specialized chemical synapses called NMJs (NeuroFIG 2D and NeuroFIG 21 also see Muscle system - Introduction). The anatomical features of these synapses are essentially the same as those for chemical synapses between neurons however, one distinction is the basal lamina that separates the presynaptic motor neuron and the postsynaptic muscle. Basal-lamina-associated proteins nidogen/entactin (NID-1) and type XVIII (CLE-1) collagen are enriched near synaptic contacts. Nidogen is concentrated between the nerve cords and muscles, whereas CLE-1 is concentrated above the regions in which NMJs form (Ackley et al., 2003). Mutations in these basal lamina proteins lead to defects in the organization of NMJs. In contrast to most other organisms, muscles extend long, thin processes (arms) to nerve bundles to make synapses with the motor neurons in C. elegans. In many cases, chemical synapses onto muscle arms occur in specialized zones where several muscles extend arms that interdigitate to form a &ldquomuscle plate&rdquo around a presynaptic specialization so that vesicle release from a single axon can simultaneously stimulate more than one muscle (White et al., 1976, 1986 Liu et al., 2006). In addition, there are often gap junctions between these muscle arms. For example, along the VNC and DC, muscle arms crowd around the presynaptic varicosities of the motor neurons to receive simultaneous input. Besides the VNC and DC, NMJs are also concentrated on the inside surface of the NR where muscle arms from head muscle rows arrange into a circumferential muscle plate. Unlike somatic muscles, pharyngeal muscles do not form arms, and presynaptic processes are often embedded directly in the muscle soma. In the male tail, presynaptic motor axons often terminate at the synapse, and again, contact is sometimes made directly onto the muscle soma for certain sex muscles.
2.10.3 Electrical Synapses
Electrical synapses, or gap junctions (GJs), form by close contact between cells. They are found virtually in all tissues of C. elegans, and essential for embryogenesis (Phelan 2005). In the nervous system, gap junctions are made between neurons and between muscle cells (but not between neurons and muscle cells as they are generally separated by a basal lamina.) The adult C. elegans nervous system has about 600 highly reproducible neuronal gap junctions, in addition to the 5000 predicted chemical synapses (White et al., 1986). The number of gap junctions throughout the life cycle of the animal is likely much higher as some neuronal gap junctions are assembled during embryonic development but are remodeled in early larval stages and dissolved by the adult stage (Chuang et al., 2007). Between neurons, axon-to-axon and axosomatic contacts are common soma-to-soma contacts are less common. Electrical synapses can occur at any locale within the nervous system they are not restricted to any neuropil. These synapses may affect behavioral events by synchronizing neuronal activity, by cross-inhibition of neighboring axons, or by relaying signals along neighboring segmental regions from one homolog to another. Alternately, the gap junction may transmit metabolic signals. Some GJs have a developmental role in halting axon outgrowth when two homologous axons establish the limits of their neighboring territories, an event known as contact termination (White et al., 1986). These GJs between homologs are very common many bilateral neuron pairs in the head encircle only half of the NR (cf. ASH, ASI, ASJ, etc.), because they stop when they encounter the process of their functional homolog to form a GJ. This property is also seen in VD motor neurons along the VNC. Important synaptic connections in the VNC can involve GJs between a command interneuron (AVA or AVB) and the cell body of a motor neuron (White et al., 1976, 1986). Other functions for gap junctions include regulation of asymmetric gene expression in a neuron pair and synchronization of neuron and muscle activities (e.g., synchronization of action potentials and Ca ++ transients in body-wall muscle, Ca ++ wave propogation during defecation motor program, facilitation of intermuscular electrical coupling for synchronous pharyngeal muscle contractions, transmission of signals among male-specific muscles during male copulation) (Liu et al, 2011a Liu et al., 2011b Chuang et al., 2007 Peters et al., 2007, Li et al, 2003). During embryogenesis transient gap junction networks may regulate formation of nascent circuits (Chuang et al., 2007).
GJs in nematodes are formed by intramembrane proteins called &ldquoinnexins,&rdquo which are completely different in their amino acid sequence from the vertebrate &ldquoconnexins.&rdquo Instead, they are the homologs of vertebrate "pannexins" (Starich et al., 1996 Phelan and Starich, 2001 Altun et al., 2009). They may coassemble to form homotypic, heterotypic and heteromeric gap junctions (NeuroFIG 22). Additionally, these molecules may form hemichannels that connect a cell&rsquos interior to the extracellular space, providing a pathway for release and uptake of molecules and ions in a controlled manner. In addition to eat-5, unc-7, and unc-9, which had been discovered previously through mutant analyses, the completion of genomic sequencing of C. elegans revealed 22 more innexin genes (C. elegans Sequencing Consortium, 1998 Bargmann, 1998). These additional innexins were numbered arbitrarily from inx-1to inx-22. Further sequencing and genomic analysis of two additional Caenorhabditis species (C. briggsae and C. remanei) revealed that each of these species has retained at least one member of each type of these innexins, except inx-8 and inx-9, which share a single ortholog in C. briggsae, but have distinct orthologs in C. remanei (see Wormbase). This strongly suggests that each innexin gene is a true gene rather than a pseudogene. Among C. elegans innexins, there are 3 sets of polycistronic ones: inx-12 and inx-13, inx-16 and inx-17, and inx-21, and inx-22. Individual GJs in neurons can involve heteromeric channels made from several different innexin subunits. Neuronal GJs differ from those in other nematode tissues by showing equal numbers of intramembrane particles in both the &ldquoE-face&rdquo and &ldquoP-face&rdquo (Hall, 1987). Through expression analyses all innexins except inx-5, inx-15, inx-16, inx-20, inx-21, inx-22, and eat-5 were found in the C. elegans nervous system (Altun et al., 2009). Among these, the most widely expressed innexins were inx-7, unc-7, and unc-9, while the least widely expressed ones were inx-1, inx-2, and inx-11. Also, TEM analyses revListealed that gap junctions exist between glia (socket and sheath cells) and hypodermis as well as between the socket and sheath cells, but not between glia and neurons (Altun et al., 2009).
Use drop down menus to go to individual neuron pages.
Ackley, B.D., Kang, S.H., Crew, J.R., Suh, C., Jin, Y. and Kramer, J.M. 2003. The basement membrane components nidogen and type XVIII collagen regulate organization of neuromuscular junctions. J. Neurosci. 23: 3577-3587. Article
Albeg, A., Smith, C.J., Chatzigeorgiou, M., Feitelson, D.G., Hall, D.H., Schafer, W.R., Miller, D.M. and Treinin, M. 2011. C. elegans multidendritic sensory neurons: morphology and function. Mol. Cell. Neurosci. 46: 308-317. Article
Albertson, D.G. and Thomson, J.N. 1984. The pharynx of C. elegans. Phil. Trans. Royal Soc. London 275B: 299-325. Article
Alcedo, J. and Kenyon, C. 2004. Regulation of C. elegans longevity by specific gustatory and olfactory neurons. Neuron 41: 45&ndash55. Article
Altun-Gultekin, Z.F., Andachi Y., Tsalik, E.L., Pilgrim, D., Kohara, Y. and Hobert, O. 2001. A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23, controls cell fate specification of a defined interneuron class in C. elegans. Development 128: 1951-1969. Article
Altun, Z.F., Chen, B., Wang, Z-W. and Hall, D. H.. 2009. High resolution map of Caenorhabditis elegans gap junction proteins. Dev. Dyn. 238: 1936-1950. Article
Antebi, A., Norris, C.R., Hedgecock E.M. and Garriga G. 1997. Cell and growth cone migrations. In C. elegans II (ed. D.L. Riddle et al.), pp. 583&ndash609. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. Article
Appelby, P. A. 2012. A model of chemotaxis and associative learning in C. elegans.Biological Cybernetics. 106: 373-387. Article
Arnadottir, J., and Chalfie, M. 2010. Eukaryotic mechanosensitive channels. Ann. Rev. Biophysics. 39: 111-137. Article
Aurelio, O., Hall, D.H. and Hobert, O. 2002. Immunoglobulin-domain proteins required for maintenance of ventral nerve cord organization. Science. 295: 689-690. Abstract
Avery, L. and Thomas, J.H. 1997. Feeding and defecation. In C. elegans II (ed D.L. Riddle et al.), pp. 678&ndash716. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. Article
Bargmann, C.I., and Avery, L. 1995. Laser killing of cells in Caenorhabditis elegans: Modern biological analysis of an organism (ed. Epstein, H.F. and Shakes, D.C.). Chapter 10. pp 225-249. Academic Press, California. Abstract
Bargmann, C.I. 1998. Neurobiology of the Caenorhabditis elegans Genome. Science 282: 2028-2033. Article
Bargmann, C.I. 2006. Chemosensation in C. elegans. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.123.1. Article
Bargmann, C.I and Horvitz, H.R. 1991. Control of larval development by chemosensory neurons in Caenorhabditis elegans. Science 251: 1243-1246. Abstract
Bargmann, C.I., Hartwieg, E. and Horvitz, H.R. 1993. Odorant-selective genes and neurons mediate olfaction in C. elegans. Cell 74: 515&ndash 27. Abstract
Bargmann, C.I. and Mori, I. 1997. Chemotaxis and thermotaxis. In C. elegans II (ed. D.L. Riddle et al.), pp. 717&ndash737. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. Article
Barr, M.M. and Garcia, L.R. 2006. Male mating behavior. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.7.1. Article
Bergamasco, C. and Bazzicalupo, P. 2006. Chemical sensitivity in C. elegans. Cell Mol. Life Sci. 63: 1510-1522. Abstract
Bird, A.F. and Bird. J. 1991. The structure of nematodes. Academic Press, California.
Bounoutas, A. and Chalfie, M. 2007. Touch sensitivity in Caenorhabditis elegans. European J. Physiol. 454: 691-702. Article
Bretscher, J., Busch, K.E. and de Bono, M. 2008. A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 105: 8044-8049. Article
Bretscher, J.A., Kodama-Namba, E., Busch, K.E., Murphy, R.J., Soltesz, Z., Laurent, P. and de Bono, M. 2011. Temperature, oxygen, and salt-sensing neurons in C. elegans are carbon dioxide sensors that control avoidance behavior. Neuron 69: 1099-1113. Article
Bülow, H.E. and Hobert, O. 2006. The molecular diversity of glycosaminoglycans shapes animal development. Annu Rev. Cell Dev. Biol. 22: 375-407. Abstract
Bülow, H.E., Berry, K.L., Topper, L.H., Peles, E. and Hobert O. 2002. Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1. Proc. Natl. Acad. Sci. 99: 6346-6351. Article
Burr, A.H.J. 1985. The photomovement of C. elegans , a nematode which lacks ocelli. Proof that the response is to light not radiant heating. Photochem. Photobiol. 41: 577-582. Abstract
Chalfie, M. 1993. Touch receptor development and function in Caenorhabditis elegans. J. Neurobiol. 24: 1433-1441. Abstract
Chalfie, M. and Sulston, J.E. 1981. Developmental genetics of the mechanosensory neurons of C. elegans. Dev. Biol. 82: 358-370. Abstract
Chalfie, M. and Thomson, J.N. 1979. Organization of neuronal microtubules in the nematode Caenorhabditis elegans. J. Cell Biol. 82: 278-289. Article
Chalfie, M. and Thomson, J.N. 1982. Structural and functional diversity in the neuronal microtubules of Caenorhabditis elegans. J. Cell Biol. 93: 15-23. Article
Chalfie M. and White J. 1988. The nervous system. In The nematode C. elegans (ed. W.B. Wood), pp. 337&ndash391. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. Abstract
Chalfie, M., Sulston, J.E., White, J.G., Southgate, E., Thomson, J.N. and Brenner, S. 1985. The neural circuit for touch sensitivity in Caenorhabditis elegans. J. Neurosci. 5: 956-964. Article
Chang, A.J., Chronis, N., Karow, D.S., Marletta, M.A. and Bargmann, C.I. 2006. A distributed chemosensory circuit for oxygen preference in C. elegans. PLoS Biol 4: e274. Article
Chatzigeorgiou, M. and Schafer, W.R.. 2011. Lateral facilitation between primary mechanosensory neurons controls nose touch perception in C. elegans. Neuron 70: 299-309. Article
Chatzigeorgiou, M. Yoo, S., Watson, J.D., Lee, W.H., Spencer, W.C., et al. 2010. Specific roles for DEG/ENaC and TRP channels in touch and thermosensation in C. elegansnociceptors. Nat. Neurosci.13: 861-868. Article
Chen, B.L., Hall, D.H. and Chklovskii, D.B. 2006. Wiring optimization can relate neuronal structure and function. Proc. Natl. Acad. Sci. 103: 4723-4728. Article
Cheung, B.H.H., Arellano-Carbajal, F., Rybicki, I. and De Bono, M. 2004. Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior. Curr. Biol. 14: 1105-1111. Article
Cheung, B.H.H., Cohen, M., Rogers, C., Albayram, O. and De bono, M. 2005. Experience-dependent modulation of C. elegans behavior by ambient oxygen. Curr. Biol. 15: 905&ndash917. Article
Chiba, C.M. and Rankin C.H. 1990. A developmental analysis of spontaneous and reflexive reversals in the nematode Caenorhabditis elegans. J. Neurobiol. 21: 543-554. Article
Chisholm, A.D. and Jin, Y. 2005. Neuronal differentiation in C. elegans. Curr. Op. Cell Biol. 17: 682-689. Abstract
Chitwood, B.G. and Chitwood, M.B. 1950. The nervous system. In An introduction to nematology, pp. 160&ndash174. University Park Press, Baltimore.
Chuang, C-F., VanHoven, M. K., Fetter, R. D., Verselis, V. K. and Bargmann, C. I. 2007. An innexin-dependent network establishes left-right neuronal asymmetry in C. elegans. Cell. 129: 787-799. Article
Culotti, J.G. and Russell, R.L. 1978. Osmotic avoidance defective mutants of the nematode Caenorhabditis elegans. Genetics 90: 243-256. Article
Croll, N.A. 1975. Components and patterns in the behavior of the nematode Caenorhabditis elegans. J. Zoology 176: 159&ndash176. Abstract
Davis, R.E. and Stretton, A.O.W. 1992. Extracellular recordings from the motor nervous system of the nematode, Ascaris suum. J. Comp. Physiol. 171: 17-28. Abstract
De Bono, M. 2003. Molecular approaches to aggregation behavior and social attachment. J. Neurobiol. 54: 78-92. Article
De Bono, M. and Maricq, A.V. 2005. Neuronal substrates of complex behaviors in C. elegans. Ann. Rev. Neurosci. 28: 451-501. Article
Driscoll, M. and Kaplan, J. 1997. Mechanotransduction. In C. elegans II (ed. D.L. Riddle et al.), pp. 645&ndash677. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York. Article
Durbin, R.M. 1987. &ldquoStudies on the development and organisation of the nervous system of C. elegans.&rdquo Ph.D. thesis. University of Cambridge, United Kingdom. Article
Emmons, S.W. 2005. Male development. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.33.1. Article
Emmons, S.W. and Lipton, J. 2003. Genetic basis of male sexual behavior. J. Neurobiol. 54: 93-110. Article
Faumont, S., Miller, A.C. and Lockery, S.R. 2005. Chemosensory behavior of semi-restrained Caenorhabditis elegans. J. Neurobiol. 65: 171&ndash178. Abstract
Fukushige, T., Siddiqui, Z.K., Chou, M. and Culotti, J.G. 1999. MEC-12, an alpha-tubulin required for touch sensitivity in C. elegans. J. Cell Sci. 112: 395-403. Article
Gally, C., Eimer, S., Richmond, J.E. and Bessereau, J.L. 2004. A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans. Nature 431: 578-582. Abstract
García-Añoveros, J., García, J. A., Liu, J-D. and Corey, D. P. 2000. The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations. Neuron. 20: 1231-1241. Article
Giles, A.C., Rose, J.K. and Rankin, C.H. 2006. Investigations of learning and memory in Caenorhabditis elegans. Int. Rev. Neurobiol. 69: 37-71. Abstract
Goodman, M.B. 2006. Mechanosensation. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.62.1. Article
Goodman, M.B. and Schwarz, E.M. 2003. Transducing touch in Caenorhabditis elegans. Annu. Rev. Physiol. 65: 429&ndash452. Abstract
Goodman, M.B., Hall, D.H., Avery, L. and Lockery, S.R. 1998. Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron 20: 763-772. Article
Gray, J.M., Hill, J.J. and Bargmann, C.I. 2005. A circuit for navigation in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 102: 3184-3191. Article
Gray J.M., Karow, D.S., Lu, H., Chang, A.J., Chang, J.S., Ellis, R.E., Marletta, M A. and Bargmann, C I. 2004. Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430: 317-322. Abstract
Gu, G., Caldwell, G.A. and Chalfie, M. 1996. Genetic interactions affecting touch sensitivity in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 93: 6577&ndash6582. Article
Halevi, S., McKay, J., Palfreyman M., Yassin, L., Eshel, M., Jorgensen, E. and Treinin, M. 2002. The C.elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. 21: 1012&ndash1020. Article
Hall D.H. 1977. &ldquoThe posterior nervous system of the nematode Caenorhabditis elegans.&rdquo Ph.D. thesis. California Institute of Technology, Pasadena.
Hall D.H. 1987. Freeze-fracture and freeze-etch studies of the nematode Caenorhabditis elegans. Ann. N.Y. Acad. Sci. 494: 215&ndash217. Abstract
Hall, D.H. and Hedgecock, E.M. 1991. Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans. Cell 65: 837-847. Abstract
Hall, D.H. and Russell, G.J. 1991. The posterior nervous system of the nematode Caenorhabditis elegans: Serial reconstruction of identified neurons and complete pattern of synaptic interactions. J. Neurosci. 11: 1-22. Article
Hall, D.H., Lints, R. and Altun, Z. 2006. Nematode neurons: anatomy and anatomical methods in Caenorhabditis elegans. Int. Rev. Neurobiol. 69: 1-35. Abstract
Hallem, E.A. and Sternberg, P.W. 2008. Acute carbon dioxide avoidance in Caenorhabditis elegans. Proc. Natl. Acad. Sci.105: 8038-8043. Article
Hardaker, L.A., Singer, E., Kerr, R., Zhou, G. and Schafer, W.R. 2001. Serotonin modulates locomotory behavior and coordinates egg-laying and movement in Caenorhabditis elegans. J. Neurobiol. 49: 303-313. Abstract
Hart, A.C., Sims, S. and Kaplan, J.M. 1995. Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor. Nature 378: 82-85. Abstract
Hart, A.C., Kass, J., Shapiro, J.E. and Kaplan, J.M. 1999. Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron. J. Neurosci. 19: 1952-1958. Article
Hedgecock, E.M. and Russell, R.L. 1975. Normal and mutant thermotaxis in the nematode Caenorhabditis elegans. Proc. Natl. Acad. Sci. 72: 4061&ndash4065. Article
Hedgecock, E.M., Culotti, J.G. and Hall, D.H. 1990. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4: 61-85. Abstract
Hedgecock, E.M., Culotti, J.G., Thomson, J.N. and Perkins, L. A. 1985. Axonal guidance mutants of Caenorhabditis elegans identified by filling sensory neurons with fluorescein dyes. Dev. Biol. 111: 158-170. Abstract
Hedgecock, E.M., Culotti, J.G., Hall, D.H. and Stern, B. D. 1987. Genetics of cell and axon migrations in Caenorhabditis elegans. Development. 100: 365-382. Article
Herman, R.K. 2005. Touch sensation in Caenorhabditis elegans. Bioessays 18: 199-206. Abstract
Hilliard, M., Bargmann, C.I. and Bazzicalupo, P. 2002. C. elegans responds to chemical repellents by integrating sensory inputs from the head and the tail. Curr. Biol. 12: 730-734. Article
Hobert, O. and Bülow, H. 2003. Development and maintenance of neuronal architecture at the ventral midline of C. elegans. Curr. Op. Neurobiol. 13: 70-78. Abstract
Hutter, H. 2003. Extracellular cues and pioneers act together to guide axons in the ventral cord of C. elegans. Development 130: 5307-5318. Article
Hutter, H., Wacker, I., Schmid, C. and Hedgecock, E.M. 2005. Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in C. elegans. Dev. Biol. 284: 260-272. Article
Iino, Y., and Yoshida, K. 2009. Parallel use of two behavioral mechanisms for chemotaxis in Caenorhabditis elegans. J Neurosci. 29:5370-5380. Article
Inada, H., Ito, H., Satterlee, J., Sengupta, P., Matsumoto, K. and Mori, I. 2006. Identification of guanylyl cylases that function in thermosensory neurons of Caenorhabditis elegans. Genetics. 172: 2239-2252. Article
Jacob, T.C. and Kaplan, J.M. 2003. The EGL-21 Carboxypeptidase E Facilitates Acetylcholine Release at Caenorhabditis elegans Neuromuscular Junctions. J. Neurosci. 23: 2122. Article
Jeong P.Y., Jung M., Yim, Y.H., Kim, H., Park, M., Hong, E., Lee, W., Kim, Y.H., Kim, K. and Paik, Y.K. 2005. Chemical structure and biological activity of the Caenorhabditis elegans dauer-inducing pheromone. Nature 433: 541-545. Abstract
Jin, Y. 2002. Synaptogenesis insights from worm and fly. Curr. Opin. Neurobiol.12: 71-79. Abstract
Jin, Y. 2005. Synaptogenesis. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.44.1. Article
Jorgensen E.M. 2006. GABA. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.14.1. Article
Jorgensen, E.M. and Nonet, M.L. 1995. Neuromuscular junctions in the nematode C. elegans. Semin. Dev. Biol. 6: 207-220. Abstract
Jospin, M., Mariol, M.C., Segalat, L. and Allard, B. 2004. Patch clamp study of the UNC-105 degenerin and its interaction with the LET-2 collagen in Caenorhabditis elegans muscle. J. Physiol. 557: 379-388. Article
Kahn-Kirby, A.H. and Bargmann, C.I. 2006. Trp channels in C. elegans. Annu. Rev. Physiol. 68: 719-736. Abstract
Kaplan, J. M. and Horvitz, H. R. 1993. A dual mechanosensory and chemosensory neuron in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 90:2227-2231. Article
Knobel, K.M., Davis, W.S., Jorgensen, E.M. and Bastiani, M.J. 2001. UNC-119 suppresses axon branching in C. elegans. Development 128: 4079-4092. Article
Kuhara, A., Inanda, H., Katsura, I. and Mori, I. 2002. Negative regulation and gain control of sensory neurons by the C. elegans calcineurin TAX-6. Neuron 33: 751-763. Article
Kuhara, A., Okumura, M., Kimata, T., Tanizawa, Y., Takano, R., Kimura, K. D., Inada, H., Matsumoto, K. and Mori, I. 2008 Temperature sensing by an olfactory neuron in a circuit controlling behavior of C. elegans. Science 320: 803-807. Article
Li, S., Dent, J. A., and Roy, R. 2003. Regulation of intermuscular electrical coupling by the Caenorhabditis elegans innexin inx-6. Mol. Biol. Cell 14:2630-2644. Abstract
Li, W., Feng, Z., Sternberg, P.W. and Shawn Xu, X.Z. 2006. A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue. Nature 440: 684-687. Abstract
Lipton, J. and Emmons, S.W. 2003. Genetic basis of male sexual behavior. J. Neurobiol. 54: 93-110. Article
Lithgow, G., White, T., Melov, S. and Johnson, T. 1995.Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc. Nat. Acad. Sci. 92: 7540-7544. Abstract
Liu, J., Schrank, B. and Waterston, R.H. 1996. Interaction between a putative mechanosensory membrane channel and a collagen. Science 273: 323-324. Abstract
Liu, K.S. and Sternberg, P.W. 1995. Sensory regulation of male mating behavior in Caenorhabditis elegans. Neuron 14: 79&ndash89. Article
Liu, P., Chen, B. and Wang, Z-W. 2011a. Gap junctions synchronize action potentials and Ca 2+ transients in Caenorhabditis elegans body wall muscle. PLoS Genet 7: e1001326.. Article
Liu, Y., LeBeouf, B., Guo, X., Correa, P. A., Gualberto, D., Lints, R. and Garcia, R. L. 2011b. A cholinergic-regulated circuit coordinates the maintenance and bi-stable states of a sensory-motor behavior during Caenorhabditis elegans male copulation. J. Biol. Chem .286: 44285-44293. Article
Liu, Q. Chen, B., Hall, D.H. and Wang, Z-W. 2006. A quantum of neurotransmitter causes minis in multiple postsynaptic cells at the Caenorhabditis elegans neuromuscular junction. J. Neurobiol. 67: 123-128. Abstract
Liu, S., Schulze, E. and Baumeister, R. 2012. Temperature- and touch-sensitive neurons couple CNG and TRPV channel activities to control heat avoidance in Caenorhabditis elegans. PLoS ONE 7: e32360doi:10.1371/journal.pone.0032360. Article
McIntire, S.L., Jorgensen, E., Kaplan, J. and Horvitz, H.R. 1993. The GABAergic nervous system of Caenorhabditis elegans. Nature 364: 337-341. Abstract
Melkman, T. and Sengupta, P. 2004. The worm&rsquos sense of smell. Development of functional diversity in the chemosensory system of Caenorhabditis elegans. Dev. Biol. 265: 302-319. Article
Mellem, J.E., Brockie, P.J., Zheng, Y., Madsen, D.M., Maricq, A.V. 2002. Decoding of polymodal sensory stimuli by postsynaptic glutamate receptors in C. elegans. Neuron 36: 933-944. Article
Montell, D.J. 1999. The genetics of cell migration in Drosophila melanogaster and Caenorhabditis elegans development. Development 126: 3035-3046. Article
Mori, I. and Ohshima, Y. 1995. Neural regulation of thermotaxis in Caenorhabditis elegans. Nature 376: 344&ndash348. Abstract
Mori, I. 1999. Genetics of chemotaxis and thermostaxis in the nematode Caenorhabditis elegans. Annu. Rev. Genet. 33: 399-422. Abstract
Nakata, K., Abrams, B., Grill, B., Goncharov, A., Huang, X., Chisholm, A.D. and Jin, Y. 2005. Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell 120: 407-420. Article
O&rsquoHagan, R. and Chalfie, M. 2006. Mechanosensation in Caenorhabditis elegans. Int. Rev. Neurobiol. 69: 169-203. Abstract
Ohnishi, A., Kuhara, A., Nakamura, F., Okochi, Y. and Mori, I. 201.1 Bidirectional reulation of thermotaxis by glutamate transmission in Caenorhabditis elegans. Embo J. 30: 1376-1388. Article
Perkins, L.A., Hedgecock, E.M., Thomson, J.N., Culotti, J.G. 1986. Mutant sensory cilia in the nematode C. elegans. Dev. Biol. 117: 456-487. Abstract
Peters, M. A., Teramoto, T., White, J. Q., Iwasaki, K.,and Jorgensen, E. M. 2007. A calcium wave mediated by gap junctions coordinates a rhythmic behavior in C. elegans. Curr. Biol. 17: 1601-1608. Article
Phelan, P. and Starich, T.A. 2001. Innexins get into the gap. Bioessays 23: 388-396. Abstract
Phelan, P. 2005. Innexins: members of an evolutionarily conserved family of gap-junction proteins. Biochim. Biophys. Acta 1711:225-245. Article
Pierce-Shimomura, J.T., Morse, T.M. and Lockery, S. 1999. The fundamental role of pirouettes in Caenorhabditis elegans chemotaxis. J. Neurosci. 19: 9557-9569. Article
Pierce-Shimomura, J.T., Faumont, S., Gaston, M.R., Pearson, B.J. and Lockery, S.R. 2001. The homeobox gene lim-6 is required for distinct chemosensory representations in C. elegans. Nature 410: 694&ndash698. Abstract
Ren, X-C., Kim, S.K., Fox, E., Hedgecock, E.M. and Wadsworth, W.G. 1999. Role of netrin UNC-6 in patterning the longitudinal nerves of Caenorhabditis elegans. J. Neurobiol. 39:107-118. Abstract
Richmond, J.E. and Broadie, K.S. 2002. The synaptic vesicle cycle: exocytosis and endocytosis in Drosophila and C. elegans. Curr. Op. Neurobiol. 12: 499-507. Abstract
Riddle, D.L. and Golden, J.W. 1982. A pheromone influences larval development in the nematode C. elegans. Science 218: 578-580. Abstract
Rittenburg, N. and Baumeister, R. 1999. Thermal avoidance in Caenorhabditis elegans: an approach to the study of nociception. Proc. Nat. Acad. Sci. 96: 10477-10482. Article
Rogers, C., Persson, A., Cheung B. and de Bono, M. 2006. Behavioral Motifs and Neural Pathways Coordinating O2 Responses and Aggregation in C. elegans. Curr. Biol. 16: 649-659. Article
Rolls, M.M., Hall, D.H., Victor, M., Rapoport, T.A. and Stelzer, E.H. 2002. Targeting of rough endoplasmic reticulum membrane proteins and ribosomes in invertebrate neurons. Mol. Biol. Cell 13: 1778-1791. Article
Rostaing, P., Weimer R.M., Jorgensen, E.M., Triller, A. and Bessereau, J-L. 2004. Preservation of immunoreactivity and fine structure of adult C. elegans tissues using high-pressure freezing. J. Histochem. Cytochem. 52: 1-12. Article
Ryu WS, Samuel AD. 2002. Thermotaxis in Caenorhabditis elegans analyzed by measuring responses to defined thermal stimuli. J. Neurosci. 22:5727&ndash33. Article
Salser, S.J. and Kenyon, C. 1992. Activation of a C. elegans Antennapedia homologue in migrating cells controls their direction of migration. Nature 355: 255-258. Abstract
Sambongi, Y., Nagae, T., Liu, Y., Yoshimizu, T., Takeda, K., Wada, Y. and Futai, M. 1999. Sensing of cadmium and copper ions by externally exposed ADL, ASE, and ASH neurons elicits avoidance response in Caenorhabditis elegans. Neuroreport 10: 753&ndash757. Abstract
Sasakura, H., Inada, H., Kuhara, A., Fusaoka, E., Takemoto, D., Takeuchi, K. and Mori, I. 2005. Maintenance of neuronal positions in organized ganglia by SAX-7, a Caenorhabditis elegans homologue of L1. EMBO J. 24: 1477-1488. Article
Sawin, E.R., Ranganathan, R. and Horvitz, H.R. 2000. C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway. Neuron 26: 619-631. Article
Schafer, W.R. 2005. Egg-laying. In WormBook (ed. The C. elegans Research Community), WormBook, doi/10.1895/wormbook.1.38.1. Article
Sharabi, K, Hurwitz, A., Simon, A.J.,Beitel, G.J., Morimoto, R.I., Rechavi, G., Sznajder, J.I. and Gruenbaum, Y. 2009. Elevated CO2 levels affect development, motility, and fertility and extend life span in Caenorhabditis elegans. Proc. Natl. Acad. Sci. 106: 4024-4029. Article
Starich, T.A., Lee, R.Y.N., Panzarella, C., Avery, L. and Shaw, J.E. 1996. eat-5 and unc-7 represent a multigene family in Caenorhabditis elegans involved in cell-cell coupling. J. Cell Biol. 134: 537-548. Article
Sulston, J.E. 1976. Post-embryonic development in the ventral cord of C. elegans. Philos. Trans. R. Soc. Lond. Series B. Biol. Sci. 275: 287-298. Article
Sulston, J.E. and Horvitz, H.R. 1977. Post-embryonic cell lineages of the nematode Caenorhabditis elegans. Dev. Biol. 56: 110-156. Article
Sulston, J.E., Albertson, D.G. and Thomson, J.N. 1980. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev Biol. 78: 542-576. Article
Sulston, J.E., Schierenberg, E., White, J.G. and Thomson, J.N. 1983. The embryonic cell lineage of the nematode Caenorhabditis elegans. Dev. Biol. 100: 64-119. Article
Syntichaki, P. and Tavernarakis, N. 2004. Genetic models of mechanotransduction: the nematode Caenorhabditis elegans. Physiol. Rev. 84: 1097-1153. Article
Tavernarakis, N., Shreffler, W., Wang, S.L. and Driscoll M.A. 1997. unc-8, a DEG/ENaC family member, encodes a subunit of a candidate mechanically gated channel that modulates C. elegans locomotion. Neuron 18: 107-119. Article
Tobin, D.M. and Bargmann, C.I. 2004. Invertebrate nociception: behaviors, neurons and molecules. J. Neurobiol. 61: 161-174. Article
Troemel, E.R., Kimmel, B.E., Bargmann, C.I. 1997. Reprogramming chemotaxis responses: sensory neurons define olfactory preferences in C. elegans. Cell 91: 161&ndash169. Article
Tsalik, E.L., Niacaris, T., Wenick, A.S., Pau, K., Avery, L. and Hobert, O. 2003. LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system. Dev. Biol. 263: 81&ndash102. Article
Van Voorhies, W.A. and Ward, S. 2000. Broad oxygen tolerance in the nematode Caenorhabditis elegans. J. Exp. Biol. 203: 2467-2478. Article
Von Stetina, S.E., Treinin, M., and Miller III, D.M. 2006. The motor circuit. Int. Rev. Neurobiol. 69: 125-167. Abstract
Wadsworth, W.G. and Hedgecock, E.M. 1996. Hierarchical guidance cues in the developing nervous system of C. elegans. Bioessays 18: 355-362. Abstract
Wadsworth, W.G., Bhatt, H. and Hedgecock, E.M. 1996. Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16: 35-46. Article
Walthall, W.W. and Chalfie, M.1988. Cell-cell interactions in the guidance of late-developing neurons in C. elegans. Science. 239: 643-645. Abstract
Walthall, W.W., Li, L., Plunkett, J.A. and Hsu, C.Y. 1993. Changing synaptic specifications in the nervous system of Caenorhabditis elegans - Differentiation of the DD motoneurons. J. Neurobiol. 24: 1589-1599. Abstract
Ward, S., Thomson, J., White, J. and Brenner, S. 1975. Electron microscopical reconstruction of the anterior sensory anatomy of the nematode C. elegans. J. Comp. Neurol. 160: 313-337. Article
Ware, R.W., Crossland, K., Russell, R.L. and Clark, D.V. 1975. The nerve ring of the nematode C. elegans: Sensory input and motor output. J. Comp. Neurol. 162: 71-110. Article
Way, J.C. and Chalfie, M. 1989. The mec-3 gene of Caenorhabditis elegans requires its own product for maintained expression and is expressed in three neuronal cell types. Genes Develop. 3: 1823-1833. Article
Weimer, R.M. and Jorgensen, E. M. 2003. Controversies in synaptic vesicle exocytosis. J. Cell Science 116: 3661-3666. Article
Wes, P.D. and Bargmann, C.I. 2001. C. elegans odour discrimination requires asymmetric diversity in olfactory neurons. Nature 410: 698-701. Abstract
White, J.G., Albertson, D.G. and Anness M.A.R. 1978. Connectivity changes in a class of motoneurone during the development of a nematode. Nature 271: 764-766. Abstract
White J.G., Southgate, E., Thomson, J.N. and Brenner, S. 1976. The structure of the ventral nerve cord of Caenorhabditis elegans. Philos. Trans. R. Soc. Lond. Series B. Biol. Sci. 275B: 327-348. Article
White, J.G., Southgate, E., Thomson, J.N. and Brenner, S. 1983. Factors that determine connectivity in the nervous system of C. elegans. Cold Spring Harbor Symp. Quant. Biol. 48: 633-640. Article
White, J.G., Southgate, E., Thomson, J.N. and Brenner, S. 1986. The structure of the nervous system of the nematode C. elegans. Philos. Trans. R. Soc. Lond. Series B. Biol. Sci. 314: 1-340. Article
Wicks, S.R., Roehrig, C.J. and Rankin, C.H. 1996. A dynamic network simulation of the nematode tap withdrawal circuit: Predictions concerning synaptic function using behavioral criteria. J. Neurosci. 16: 4017-4031. Article
Yang, Y. and Lundquist, E.A. 2005. The actin-binding protein UNC115/abLIM controls formation of lamellipodia and filopodia and neuronal morphogenesis in Caenorhabditis elegans. Mol. Cell. Biol. 25: 5158-5170. Article
Zhang, Y., Lu, H. and Bargmann, C.I. 2005. Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438: 179-184. Abstract
Zhen, M. and Jin, Y. 2004. Presynaptic terminal differentiation: transport and assembly. Curr. Op. Neurobiol. 14: 280-287. Abstract