01 - 1. Synaptic transmission

1. Synaptic transmission

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1. Synaptic transmission  The presynaptic neuron synthesises, transports and stores the chemical messenger (neurotransmitter). Synthesis takes place in cell body / soma which contains the essential protein synthesis machinery. From here axonal transport occurs, and the neurotransmitter reaches the synaptic terminal. Before its eventual release, the neurotransmitter is stored within the synaptic vesicle. The release takes place through the process of membrane fusion and exocytosis.  Upon release, the neurotransmitter occupies receptors present on the surface of the postsynaptic neuronal membrane. Some of the neurotransmitter molecules will also act on autoreceptors that are present in the presynaptic neuronal membrane. Such autoreceptor activity is considered to be crucuial for feedback inhibition of the neurotransmitter synthesis and release.  Neurotransmitters exhibit specificity in receptor interaction. One neurotransmitter can have more than one receptor types, but within a given receptor site only a particular chemical conformation can be accommodated (lock and key).  Receptors have a finite number and thus get saturated if there is an over secretion of neurotransmitter.  Receptor binding is often competitive; relative synaptic concentrations of competing molecules decide the eventual degree of receptor activity. Most receptors are bound reversibly i.e. following dissociation of the neurotransmitter; the receptor falls back to its physiological status quo. Some molecules can act irreversibly producing structural alterations in the protein of receptor complexes.  After synaptic release and activity, cessation of neurotransmitter action takes place via
2. Reuptake back to presynaptic neuron via special transporters (e.g. monoamine transporters)
3. Enzymatic breakdown at the cleft (e.g. via COMT/MAO-A enzyme)
4. Removed by glia or plasma circulation (e.g. glutamate shuttle)

 Feedback control of a neurotransmitter may exist at various points

1. Control of presynaptic synthesis
2. Regulation of release
3. Reuptake regulation
4. Autoreceptor mediated presynaptic inhibition
5. Independent postsynaptic inhibition via a different neuronal network Neurotransmitters

Monoamines Amino acids Peptides Dopamine Norepinephrine Epinephrine Serotonin Acetylcholine Histamine GABA Glycine Glutamate

Endorphins Cholecystokinin Neurotensin Neuropeptide Y Leptin Ghrelin