BIO254:SynapticTransmission

Signaling across chemical synapses

The release of neurotransmitter is triggered by the arrival of a nerve impulse (or action potential) and occurs through an unusually rapid process of cellular secretion, also known as exocytosis: Within the pre-synaptic nerve terminal, vesicles containing neurotransmitter sit "docked" and ready at the synaptic membrane. The arriving action potential produces an influx of calcium ions through voltage-dependent, calcium-selective ion channels. Calcium ions then trigger a biochemical cascade which results in vesicles fusing with the presynaptic-membrane and releasing their contents to the synaptic cleft. Vesicle fusion is driven by the action of a set of proteins in the presynaptic terminal known as SNAREs. The membrane added by this fusion is later retrieved by endocytosis and recycled for the formation of fresh neurotransmitter-filled vesicles. Receptors on the opposite side of the synaptic gap bind neurotransmitter molecules and respond by opening nearby ion channels in the post-synaptic cell membrane, causing ions to rush in or out and changing the local transmembrane potential of the cell. The resulting change in voltage is called a postsynaptic potential. In general, the result is excitatory, in the case of depolarizing currents, or inhibitory in the case of hyperpolarizing currents. Whether a synapse is excitatory or inhibitory depends on what type(s) of ion channel conduct the post-synaptic current display(s), which in turn is a function of the type of receptors and neurotransmitter employed at the synapse.

Modulation of synaptic transmission

Following fusion of the synaptic vesicles and release of transmitter molecules into the synaptic cleft, the neurotransmitter is rapidly cleared from the space for recycling by specialized membrane proteins in the pre-synaptic or post-synaptic membrane. This "re-uptake" prevents "desensitization" of the post-synaptic receptors and ensures that succeeding action potentials will elicit the same size post-synaptic potential ("PSP"). The necessity of re-uptake and the phenomenon of desensitization in receptors and ion channels means that the strength of a synapse may in effect diminish as a train of action potentials arrive in rapid succession--a phenomenon that gives rise to the so-called frequency dependence of synapses. The nervous system exploits this property for computational purposes, and can tune its synapses through such means as phosphorylation of the proteins involved. The size, number and replenishment rate of vesicles also are subject to regulation, as are many other elements of synaptic transmission. For example, a class of drugs known as selective serotonin re-uptake inhibitors or SSRIs affect certain synapses by inhibiting the re-uptake of the neurotransmitter serotonin. In contrast, one important excitatory neurotransmitter, acetylcholine, does not undergo re-uptake, but instead is removed from the synapse by the action of the enzyme acetylcholinesterase.