What is meant by the term synaptic targeting?

What is meant by the term synaptic targeting?

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I am studying whether a protein interacts with the mitochondria in the synapses of neurons and I have come across the term "synaptic targeting". I am reading this paper and I have come across the following:

During synaptic development, proteins aggregate at specialized pre- and postsynaptic structures. Mechanisms that mediate protein clustering at these sites remain unknown. To investigate this process, we analyzed synaptic targeting of a postsynaptic density protein, PSD-95, by expressing green fluorescent protein- (GFP-) tagged PSD-95 in cultured hippocampal neurons.

I am not sure what exactly is meant by the term "synaptic targeting". I have tried Googling the definition but all I get are links to journal papers. I think that synaptic targeting refers to where in the synapse (e.g. presynaptic or postsynaptic ending) a protein is located, but I am not certain. Any insights are appreciated.

PSD-95 is a protein located in the post-synaptic region inside a cell. In fact it's named for this, "post synaptic density-95" referring to the dense appearance of the post synaptic area on an EM microscope and this protein's presence there.

"Synaptic targeting" in this context refers to how that protein gets to where it belongs (the synapse) in the cell, rather than just floating around in the cytoplasm by simple diffusion.

The autonomic nervous system (ANS) mediates actions that occur without voluntary control such as heart rate or blood pressure. It consists of both the sympathetic nervous system (SNS) and parasympathetic nervous systems (PNS), and they often act in a complementary manner.

In general, the sympathetic nervous system can be thought of as the pathways through which an organism responds to danger. This can include actions of running, fighting, hiding, and generally, actions used to escape predators. By contrast, the parasympathetic system controls actions related to feeding and breeding. These two systems work together to ensure that an animal can survive danger to be able to grow and reproduce successfully.

Structurally, the sympathetic nervous system consists of many nerve cells found in the peripheral and central nervous systems. This allows organisms the ability to activate many different responses at once, leading to a coordinated flight or fight response. This is important because a slow or ineffective response can lead to the death of an organism.


B.R. Mackenna MB ChB PhD FRCP(Glasg) , R. Callander FFPh FMAA AIMBI , in Illustrated Physiology (Sixth Edition) , 1990


The coordinated group action of muscles is made possible by the many synaptic connections between interneurons of the ingoing or proprioceptive neurons of one muscle group and the outgoing or motor neurons of the functionally opposite group of muscles.

This is shown diagrammatically for the reciprocal contraction and relaxation of the extensors and flexors during the stretch reflex. See also page 258 .

Reciprocal innervation is due to an inhibitory interneuron (within the spinal cord) interposed between the sensory nerve fibre and the α-motor neuron of the flexor muscle.

Reciprocal inhibition of the flexor muscle is mediated by a disynaptic (two synapses) pathway. Contraction of the extensor muscle is mediated by a monosynaptic pathway.


There’s no telling exactly what scientists will find as, neuron by synapse , they map the inner workings of our minds—but it seems all but certain great discoveries await.

At any time, an atom will have a probability to be in one state, and another probability for a different state—a bit similar to whether a neuron decides to fire or not, or a synapse will pass on data or not.

If we peer deeply into the brain, in other words, what we’ll find is that electrochemical synapse firings—produced by neurons of various types—are responsible for, as Koch puts it, the feeling of life itself, consciousness.

It’s also unclear if, and how, a hybrid synapse can work inside a living brain.

If you followed such things at the time, perhaps the phrase “Phase II report” will snap a synapse or two.

Aren't all facts, at the neuron and synapse level, really the same?

As for Cain, one wonders what synapse snapped into action there.

Inside, the cacophony of neon signs are a synapse stimulus package for your jet-lagged mind.

Maybe his secretary's two neurones would fail to synapse this morning, and she'd lose them altogether.

These are transferred from neuron to neuron through the synapse .

The contact of the axon of one neuron with the dendrons of another is called a synapse .

The place of juxtaposition of the end of one neurone against the beginning of another is called the synapse .

The simplest reflex arc consists then of a sensory neurone and a motor neurone, meeting at a synapse in a lower or reflex center.


KIF1A knockout mice died within 24 h after birth. Before death, they exhibited motor and sensory disturbances. They also showed marked decrease in the transport of synaptic vesicle precursors but not in the transport of synaptic plasma membrane precursors. Consequently, the densities of the synaptic terminals and the numbers of synaptic vesicles decreased significantly. At the same time, the knockout mice showed neuronal degeneration, which was reproduced by hippocampal neuron culture in vitro. This in vitro experiment indicated the correlation between the time course of the neuronal death in mutant mice and the time course of KIF1A expression in wild-type mice. These results demonstrate that KIF1A plays essential roles in the function, maintenance, and survival of neurons.

The decrease in the transport of synaptic vesicle precursors in the axons is consistent with our previous study (Okada et al., 1995). We have previously demonstrated with a mature peripheral nerve preparation that KIF1A associates with a class of synaptic vesicle precursors that contains synaptophysin, synaptotagmin, and Rab3A, but not SV2. KIF1A does not associate with synaptic plasma membrane precursors that contain syntaxin 1A, either. From these results, we have concluded that KIF1A transports a class of synaptic vesicle precursors but not synaptic plasma membrane precursors. This conclusion was clearly demonstrated by the sciatic nerve ligation experiment, which indicates the decreased transport of synaptotagmin and the almost normal transport of syntaxin 1A. Unfortunately, we were unable to assay the transport of SV2, a non–KIF1A-associated synaptic vesicle protein, mostly because of the technical problems. Therefore, we cannot definitely answer the question of whether SV2 transport is affected in the KIF1A knockout mice at present.

An interesting finding is that synaptic vesicles and synaptic vesicle proteins accumulate in the synapse, even when the transport of synaptic vesicle precursors are severely affected by the lack of KIF1A. One possibility is that other KIFs, unidentified KIF(s), or slightly increased conventional kinesin might partially compensate for the function of KIF1A. Another possibility is that synaptic vesicle precursors are transported by KIFs other than KIF1A in immature neurons. As shown in Fig. 7 I, inset, the expression of KIF1A increases after 8 days in culture, much later than the synapse formation and the accumulation of synaptic vesicle proteins (Fletcher et al., 1994). This suggests that synaptic vesicle precursors are transported by KIF(s) other than KIF1A in immature neurons and that the transport machinery switches to KIF1A after maturation. One candidate for this juvenile-type motor is KIF4, which is dominantly expressed in juvenile neurons and transports vesicles to the end of growing neurites (Sekine et al., 1994).

The second interesting finding is the accumulation of small clear vesicles in the cell body that are connected by fuzzy structures. These vesicles could be either precursors of synaptic vesicles that were not transported to the axon or ectopic synaptic vesicles formed most likely through ectopic exocytosis, endocytosis, and recycling underneath the plasma membrane of the cell body because precursors were not transported to the axon. In the nerve cell bodies of C. elegans unc-104 mutants, accumulation of clustered vesicles is observed, but the vesicles have denser cores and appear to be different from the vesicles observed in KIF1A mutants, although KIF1A could be the mammalian homologue of UNC-104 (Hall and Hedgecock, 1991). The reason for this difference is not clear but it may be due to differences in the types of neurons.

The third interesting finding is the neuronal death. In KIF1A mutants, axonal degeneration and degeneration of neuronal cell bodies occurred in areas of the central nervous system such as the rhinencephalon, amygdaloid area, and hippocampus. The results of in vitro culture of hippocampal neurons clearly indicated that neuronal cell death is correlated with the level of KIF1A expression in wild-type mice. In this culture system, hippocampal neurons mature and establish mature synapses after ∼8 d in culture, at which time the level of KIF1A expression in wild-type mice increases and neuronal cell death commences in KIF1A mutants. These observations clearly indicate that KIF1A is essential for the function and survival of mature neurons. Although paralyzed movement and defect of an anterograde translocation of synaptic vesicles that were observed in unc-104 mutants resemble the phenotypes of KIF1A mutant mice, the neuronal degeneration and death mentioned above were not reported for unc-104 mutants. The difference in viabilities of neurons between unc-104 and KIF1A mutants could correlate with differences in their expressions during development.

For understanding of the function of KIF1A in vivo it is important to determine the cause of neuronal cell death. One possibility is that based on the decrease in transport of precursors of mature synaptic vesicles in the KIF1A mutants and the fact that the cargoes transported by KIF1A contain some synaptic vesicle proteins involved in neurotransmitter release such as synaptotagmin and Rab3A (Okada et al., 1995), the neurotransmission at the nerve terminals is considerably impaired in the KIF1A mutants so that the electrical activities in the mutant neurons is significantly reduced, resulting in death of these neurons. In fact, coculture with wild-type cells and exposure to a low concentration of glutamate rescued the mutant cells from death in culture, consistent with this possibility.

On the other hand, the knockout mice lacking of synaptotagmin (Geppert et al., 1994a), synaptophysin (McMahon et al., 1996), or Rab3A (Geppert et al., 1994b), which cargoes transported by KIF1A were suggested to contain, and mice deficient in synapsin I or II (Rosahl et al., 1995 Takei et al., 1995), in which a marked decrease in synaptic vesicle density in the nerve terminals was observed, have been generated and reported. However, these mutant mice did not exhibit such neuronal degeneration and cell death as observed in KIF1A mutant mice. Thus, only the explanation mentioned above may not be enough to make clear about the cause of the neuronal cell death in KIF1A mutant mice. Another possibility is that KIF1A may have an additional unknown function. It may be conceivable that synaptic vesicle precursors transported by KIF1A may also contain some molecules that are essential for neuronal survival or neurotransmitter action, such as ion channel proteins, neurotrophic factors, or neurotrophic factor receptors.

Axonal degeneration similar to that observed in KIF1A mutants has also been reported for several neurodegenerative diseases such as senile dementia (Adams and Duchen, 1992). In some neurodegenerative diseases, neuronal cell death caused by defects in the transport of synaptic vesicle precursors by KIF1A may be involved. Future studies will elucidate the mechanism of neuronal degeneration and death in KIF1A mutant mice.

What is Synapse?

Neurons are the basic units of the nervous system that facilitate the impulse transmission. Neurons are not physically connected, and there is a gap between orderly arranged neurons. Synapse is the area where two neurons come closer to send and receive signals. Signals are transmitted as an action potential. When the action potential reaches the end of the first neuron (presynaptic neuron), the synapse facilitates the handover of the action potential to an adjacent neuron that is known as post synaptic neuron. Presynaptic membrane becomes positively charged, and it releases neurotransmitters into the synaptic cleft. Neurotransmitters are the chemical messengers of the nervous system. They are stored in the vesicles of the presynaptic neuron. They diffuse through the synaptic cleft and bind with the receptors located on the surface of the post synaptic membrane. Likewise action potential propagates through neurons until it receives by the target organ.

Figure 01: Synapse

The synapse is located in the ganglion. Ganglion houses millions of synapses. There are two types of synapses namely chemical synapse and electrical synapse. Chemical synapse uses chemical messengers to communicate between neurons while electrical synapse uses ion flows directly to between cells.

Part 2: Calculation of the Time Required for Diffusion of Neurotransmitter across the Synaptic Cleft


In this part, the students will estimate (a) the time it takes glutamate to diffuse from its release sites on the presynaptic membrane across the synaptic cleft to the postsynaptic membrane and (b) the rate of diffusion. For these estimations, follow steps 2–4 below.

Repeat the calculation performed in step 1, now for the Schematic Synapse Model, by assuming the distance between the apposed membranes to be 500 nm.

For both the Morphometric Synapse and the Schematic Synapse models, determine the rate of diffusion by dividing the distance (in meters) over which glutamate diffuses by the diffusion time (in seconds).

To express the rate by a more familiar measure of speed, kilometers per hour (km/h) or miles per hour (mi/h), multiply the rate determined in step 3 by a factor of 3.6 or 2.24, respectively.


Einstein's approximation equation predicts that a 25-fold increase in cleft width, from 20 nm to 500 nm, results in a 625-fold increase in diffusion time, from

378.788 μs. These diffusion times translate into mean rates of diffusion of 0.033 m/s or 0.12 km/h or 0.074 mi/h (at an assumed cleft width of 20 nm) and 0.0013 m/s or 0.0048 km/h or 0.0030 mi/h (at an assumed cleft width of 500 nm). For comparison, continuous tracking of nocturnal activity of garden snails has indicated that these animals travel at average speeds of up to 1 m/h ( they are, thus, 30 or 300 times faster than glutamate diffusing across a synaptic cleft of 20 nm or 500 nm width, respectively.

Evaluation of the Results

The above calculations provide some important perspectives. As expected from diffusion as a passive process, the rate at which glutamate diffuses across the synaptic gap is low, particularly when expressed by measures used in everyday life. However, the seemingly paradoxical situation that the glutamate molecules, nevertheless, diffuse from the presynaptic membrane to the postsynaptic membrane within an extremely short period of time can be readily resolved by taking the width of the synaptic cleft into account, which is just a few nanometers.

The calculations also help overcome a frequent misunderstanding: that the total delay time of 200 μs between the opening of the fusion pore on the presynaptic membrane and the opening of the channels associated with the glutamate receptors is due to the time it takes the transmitter molecules to diffuse across the synaptic cleft. In fact, the latter is just

1 μs and, thus, contributes rather insignificantly to the total delay time.

However, it is important for students to appreciate the fact that diffusion time increases with the square of diffusion distance. Synapses with disproportionately wide clefts, as they are depicted in the Schematic Synapse Model and in many other models used for educational purposes (without mentioning that the width of these clefts is not drawn to scale), would, if they existed, increase diffusion dramatically and delay the generation of postsynaptic potentials severely. Despite the extremely short diffusion time of glutamate at the synaptic cleft, the rate of diffusion is rather sobering – 0.074 mi/h or only 1/30th the average speed of a garden snail during nocturnal activity. At an assumed cleft width of 500 nm, it would be even more disillusioning – just 0.0030 mi/h!

In addition, the width of the synaptic cleft impacts not only neurotransmitter diffusion time but also local glutamate concentration at the postsynaptic receptor site. The latter has an important consequence. Studies have shown that high levels of glutamate are required to induce opening of the channels associated with the receptors (for reviews, see Meinrenken et al., 2003 Südhof, 2004 Lisman et al., 2007). Such high concentrations of glutamate exist in the synaptic cleft only near (within

100 nm) the site of vesicle release. Synapses with cleft widths of several hundred nanometers would, therefore, be unable to accommodate the transient, local increases in transmitter concentration required for receptor activation.

Further Reading

Now that you&rsquore all up to speed about how synaptic plasticity works and why it&rsquos so important, you might be wondering if there are any possible ways to &ldquoboost&rdquo your own brain&rsquos synaptic plasticity!

While there are no officially-approved treatments or other strategies to do this, there is some preliminary research that suggests that a wide variety of dietary compounds and supplements may have significant effects on overall synaptic plasticity.

To learn more about what these compounds are and what the latest science says about them, check out our follow-up post here.

If you’re interested in natural and targeted ways of improving your cognitive function so that you can perform optimally despite all the negative news around you, we recommend checking out SelfDecode’s Cognitive Enhancement DNA Report . It gives you genetic-based diet, lifestyle and supplement tips that can help improve your cognitive function. The recommendations are personalized based on YOUR DNA.

About the Author

Nattha Wannissorn


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Surface Tension: Definition, Explanation and Methods

In this article we will discuss about Surface Tension:- 1. Definition of Surface Tension 2. Explanation for Surface Tension 3. Method of Determination 4. Factors Affecting 5. Gibbs-Thomson Principle 6. Physiological Importance.

  1. Definition of Surface Tension
  2. Explanation for Surface Tension
  3. Method of Determination
  4. Factors Affecting
  5. Gibbs-Thomson Principle
  6. Physiological Importance

1. Definition of Surface Tension:

The force with which the surface molecules are held together is called surface tension.

2. Explanation for Surface Tension:

The interior molecules of a homogeneous liq­uid are equally attracted in all directions by surrounding molecules.

They are free to move in all directions. But the molecules in the surface of the liquid are attracted downward and sideways but not upward (except for the little attraction of air molecules).

As a result, the molecules of the sur­face are not so free to move. They are held together and form a membrane over the surface of the liquid.

Therefore, when finely powdered sulphur or other non-wetting powders are sprinkled upon water, they do not sink but are suspended on the surface.

A great part of the energy required to convert a liquid into a gas is essential to overcome surface tension and drag the molecules free from the sur­face of the liquid.

There is also an interfacial tension which is biochemically very important, especially in the process of adsorption.

This tension lies at the boundary between immiscible liquids, e.g., oil drops emulsified in water.

The tension is due to unequal attraction of the film molecules as compared with the molecules in the interior of the liquid.

Surface tension x Surface area = Surface en­ergy. A falling drop of liquid assumes a spherical form because the ratio of surface area and total free surface energy is the least.

3. Method of Determination of Surface Tension:

where, h = height of the liquid.

g = acceleration due to gravity,

r = radius of the capillary tube.

4. Factors Affecting Surface Tension:

Surface tension decreases with the increase in temperature.

2. Dissolved substances:

(a) Most inorganic salts slightly raise surface tension of water although po­tassium permanganate lowers it.

(b) Organic substances usually lower sur­face tension. Soaps and bile salts are most effective in this respect.

(c) Alkalis increase surface tension but ammonia lowers it. Strong mineral acids also decrease surface tension.

(d) In liquid-liquid and solid-liquid sys­tems, dissolved substances generally lower interfacial tension.

5. Gibbs-Thomson Principle in Relation to Surface Tension:

a. Substances that lower the surface tension become concentrated at the interface.

b. Substances that increase surface tension tend to move away from the interface.

c. Lipids and proteins which are both effec­tive in lowering surface tension are found concentrated in the cell wall.

6. Physiological Importance of Surface Tension:

Surface tension is involved in the process of diges­tion because bile salts reduce the surface tension of lipids and thus assist emulsification.

As a result, the surface area is increased which favours lipase activity on lipids.

Calcium ions (Ca 2+ )

As the functions of IP 3 and DAG indicate, calcium ions are also important intracellular messengers. In fact, calcium ions are probably the most widely used intracellular messengers.

In response to many different signals, a rise in the concentration of Ca 2+ in the cytosol triggers many types of events such as

  • muscle contraction
  • exocytosis, e.g.
    • release of neurotransmitters at synapses (and essential for the long-term synaptic changes that produce Long-Term Potentiation (LTP) and Long-Term Depression (LTD)
    • secretion of hormones like insulin

    Normally, the level of calcium in the cell is very low (

    100 nM). There are two main depots of Ca 2+ for the cell:

      The extracellular fluid (ECF &mdash made from blood), where the concentration is

    However, its level in the cell can rise dramatically when channels in the plasma membrane open to allow it in from the extracellular fluid or from depots within the cell such as the endoplasmic reticulum and mitochondria.

    Getting Ca 2+ into (and out of) the cytosol

    • Voltage-gated channels
      • open in response to a change in membrane potential, e.g. the depolarization of an action potential
      • are found in excitable cells:
        • skeletal muscle
        • smooth muscle (These are the channels blocked by drugs, such as felodipine [Plendil®], used to treat high blood pressure. The influx of Ca 2+ contracts the smooth muscle walls of the arterioles, raising blood pressure. The drugs block this.)
        • neurons. When the action potential reaches the presynaptic terminal, the influx of Ca 2+ triggers the release of the neurotransmitter.
        • the taste cells that respond to salt.
        • to the ECF by active transport using
          • an ATP-driven pump called a Ca 2+ ATPase
          • two Na + /Ca 2+ exchangers. These antiport pumps harness the energy of
            • 3 Na + ions flowing DOWN their concentration gradient to pump one Ca 2+ against its gradient and
            • 4 Na + ions flowing down to pump 1 Ca 2+ and 1 K + ion up their concentration gradients.

            How can such a simple ion like Ca 2+ regulate so many different processes? Some factors at work:

            • localization within the cell (e.g., released at one spot &mdash the T-system is an example &mdash or spread throughout the cell)
            • by the amount released (amplitude modulation, "AM")
            • by releasing it in pulses of different frequencies (frequency modulation, "FM")