Synaptic Transmission


Introduction


With over a 100 billion cells compromising the human brain and each one needing to communicate information to at least one, if not thousands of other neurons, the importance of effective coding and communication of impulses between cells is vital. In order to achieve the complexity of human cognition, perception, and movement electrical stimuli by previous cells needs to convey appropriate information to following neurons. An action potential or electrical conduction along a neuron eventually ceases at the terminal ending and requires the prorogation of a signal at the site of the post-synaptic terminal across a synapse.

Protypical Neuron Anatomy

Neurons have a round shaped Soma or Cell Body that holds the the nucleus and organelles concerned with the synthesis of protein. Dendrites are a multitude branched processes that extend from the cell body and are designed to receive signals from other cells. The Axon is a single process that carries the action potential from the nerve cell body to a target. The junction of the axon and cell body is referred to as the Axon Hillock and is the site where action potentials begin. An action potential is carried along the axon until it reaches the Terminal Ending. It is here that the synaptic transmission begins.

Different Types of Synapse

Presynaptic refers to components of a synapse specialized for transmitter release while Postsynaptic refers to those components designed for transmitter reception. There are 3 different kinds of axons that are determined by where synapse on post-synaptic cell. Axodendritic axons synapse on the dendrites of the post-synaptic cell. These cells are likely to be exhibiting an excitatory influence on the post-synaptic cells. Axosomatic axons synapse directly on the soma/cell body of the post-synaptic cell. These synapses are located closer to the axon hillock and are likely to have an inhibitory influence on the post-synaptic cell in order to "stop" propagation of an action potential. Axoaxonic axons synapse on the axons of the post-synaptic cell.

Electrical Synapses

Synapses that transmit information via the direct flow of electrical current at gap junctions are called Electrical Synapses. The membranes of the presynaptic and postsynaptic cleft are held together by paired channels in each membrane that form a Gap Junction. Ions passively flow through these pores or channels from the presynaptic to the postsynaptic channels thereby allowing the ionic current to influence the postsynaptic potential. Electrical synapse transmission has two interesting factors. Due to the size of the gap junction channels, ions are not the only substance capable of passing through them and a bidirectional flow of material is possible. The second is the speed with which electrical synapses convey information. Passive flow of ions through channels is nearly instantaneous allowing immediate response to stimulus. Electrical synapses are best adapted for regulating rhythmic or synchronized electrical activity for activities like breathing.

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Chemical Synapse

The space that separates the presynaptic and postsynaptic membranes at chemical synapses is much greater and is referred to as the Synaptic Cleft. Instead of ions flowing from the presynaptic membrane to the postsynaptic membrane, chemicals called Neurotransmitters are secreted from the presynaptic terminal and diffuse across the synaptic cleft binding to channels and other molecules in the membrane of the postsynaptic cleft. Neurotransmitters are defined by three criteria:
1. The substance must be present within the presynaptic neuron.
2. The substance must be released in response to presynaptic depolarization, and the release must be Ca2+ dependent.
3. Specific receptors for the substance must be present on the postsynaptic cell.
Membrane-bound organelles in the terminal ending called Synaptic Vesicles hold neurotransmitter until it is ready for release. The process of chemical transmission is described in a sequence of events shown in the figure. The influx of calcium via voltage-gated channels triggers the release of neurotransmitters. A rise in Ca2+ concentration causes synaptic vesicles to fuse with presynaptic membrane, releasing neurotransmitter into the synaptic cleft. Specific proteins on the surface of the synaptic vesicle and elsewhere in the presynaptic terminal called SNAREs facilitate this process.

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Neurotransmitters

Small-Molecule Transmitters are synthesized and packaged at the terminal ending by enzymes that have been carried by slow axonal transport from the cell body. After release the neurotransmitter is reabsorbed into the presynaptic terminal.
Peptide Transmitters are synthesized by the organelles of the cell body and then transported to the terminal ending using Fast Axonal Transport. This system uses microtubles and motor proteins to quickly bring peptides to their destination in order that to be modified by enzymes prior to release. The effect the neurotransmitter has on the electrical current of of the postsynaptic terminal is represented by the kind of postsynaptic potential of the membrane. Excitatory Postsynaptic Potential (EPSP) means that the membrane of the postsynaptic potential is more likely to result in carrying an action potential. Glutamate-gated channels cause an net influx of Na+ and a depolarization of the postsynaptic neuron. An Inhibitory Postsynaptic Potential (IPSP) decreases the ability of the membrane to reach threshold and carry an action potential to other areas of the cell. GABA & Glycine-gated channels cause an net influx of Cl- that hyperpolarizes the cell away from threshold.

EPSP_y_IPSP.jpg


Synapses are categorized again my their morphological characterisitcs into Gray Type I and Type II. Gray Type I synapses are usually axodendritic and have a larger Active Zones (location of the transmitter receptors), more dense postsynaptic membrane at the active zone, round synaptic vesicles, and have a larger synaptic cleft. Gray Type I are also more likely to have an excitatory effect on the postsynaptic terminal. Gray Type II synapses are usually axosomatic and have smaller active zones, less dense postsynaptic membranes at the active zone, flattened synaptic vesicles, and a more narrow synaptic cleft. Gray Type II tend to be more inhibitory in their effects on the postsynaptic cell.

Postsynaptic receptors create a EPSP or IPSP by: Ligand-Gated/Direct Gating, the transmitter reconfigures the channel when it attaches allowing for the movement of ions either in or out of the cell. Indirect Gating/Secondary Messengers, when the transmitter binds to the receptor a GTP-binding protein activates a second-messenger cascade that modulates channel activity.

Ligand-gated_vs_G-protein.jpg

Synaptic Integration

A single EPSP is not enough to begin the propagation of an action potential and often times to achieve threshold a cell most overcome IPSP influences as well. To reach threshold often requires either additional excitatory influence. This can be accomplished in two ways. Temporal Summation occurs when EPSPs occur one after another at the same site, thereby combining potential in the postsynaptic terminal. Spatial Summation is when the inputs from several presynaptic neurons acting on different areas combine to form an action potential.

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Flow Chart Review of Events

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Glossary

Axoaxonic: Axon synapses on the axons of the post-synaptic cell.
Axodendritic: axons synapse on the dendrites of the post-synaptic cell.
Axon: Neuronal process that carries the action potential from the nerve cell body to a target.
Axon Hillock: Junction of cell body and axon.
Axosomatic: axons synapse directly on the soma/cell body of the post-synaptic cell.
Dendrite: A neuronal process arising from the cell body that receives synaptic input.
Electrical Synapses: Synapses that transmit information via the direct flow of electrical current at gap junctions.
Gap Junction: A specialized intercellular contact formed by channels that directly connect the cytoplasm of two cells.
Indirect Gating/Secondary Messengers: transmitter binds to the receptor a GTP-binding protein activates a second-messenger cascade that modulates channel activity.
Ligand-Gated/Direct Gating: transmitter reconfigures the channel when it attaches allowing for the movement of ions either in or out of the cell.
Neurotransmitter: Substance released by synaptic terminals for the purpose of transmitting information from one nerve cell to another.
Postsynaptic: referring to the component of a synapse specialized for transmitter reception.
Presynaptic: referring to the component of a synapse specialized for transmitter release.
Soma/Cell Body: Holds the the nucleus and organelles concerned with the synthesis of protein.
Synaptic Cleft: Space that separates pre and post synaptic neurons at chemical synapses.
Synaptic Vesicle: Spherical, membrane-bound organelles in presynaptic terminals that store neurotransmitters.
Terminal Ending: Synaptic (often axonal) ending.

Quiz


1. Which of the following is likely to be a Gray Type I?
A. Axoaxonic
B. Axodendritic
C. Axosomatic

2. Which ion is responsible for the release of neurotransmitter into the synaptic cleft?
A. Acethycholine
B. Calcium
C. Sodium
D. Potassium

3. Which of the following is not a criteria of neurotransmitters?
A. The substance must be present within the presynaptic neuron.
B. The substance must elicit a excitatory post synaptic potential on the postsynaptic terminal.
C. The substance must be released in response to presynaptic depolarization, and the release must be Ca2+ dependent.
D. Specific receptors for the substance must be present on the postsynaptic cell.

True/False

4. Spatial Summation occurs across multiple sites.
5. Small molecule transmitters are synthesized in the cell body.
6. Ligand-gated channels are a form of second messenger channels.
7. Endocytosis is the process by which neurotransmitter is picked up into the postsynaptic cell.

Answers:

B,B,B,T,F,F,F

References:

Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. 1994. Molecular Biology of the Cell, 3rd ed. New York: Garland
Kandell, E R., J H. Schwartz, and T M. Jessell, eds. Principles of Neural Science. 4th ed. New York City: McGraw-Hill Companies, Inc., 2000.
Katz B. 1969. The Release of Neural Transmitter Substances. Springfield IL: Thomas.
Myers RD. 1994. Neuroactive peptides: unique phases in research on mammalian brain over three decades. Peptides 15(2):367-381
Nelson N, Lill H. 1994. Porters and neurotransmitter transporters. J Exp Biol 196:213-228.
Purves, D, G Augustine, D Fitzpatrick, W Hall, and A LaMantia, eds. Neuroscience. 4th ed. Sunderland, MA: Sinauer Associates, Inc., 2008.