neurotransmitterrelease

Neurotransmitter release is the process by which neurons communicate across chemical synapses. It occurs when action potentials reach the presynaptic terminal and trigger the release of neurotransmitter stored in synaptic vesicles into the synaptic cleft. Vesicles may carry different transmitters, including glutamate, GABA, acetylcholine, dopamine, serotonin, and others, and are organized at active zones to coordinate signaling.

Triggering the release begins with the arrival of an action potential, which depolarizes the presynaptic membrane and opens voltage-gated calcium channels. Influx of Ca2+ raises the intracellular calcium concentration, and Ca2+ binds to sensors such as synaptotagmin, catalyzing vesicle fusion with the plasma membrane via a SNARE complex. The core SNARE machinery includes syntaxin and SNAP-25 on the plasma membrane and synaptobrevin (VAMP) on the vesicle; regulatory proteins such as Munc13, Munc18, and complexin modulate the process.

Fusion and release involve docking, priming, and exocytosis. Vesicles may undergo full fusion, releasing most of their contents, or in some cases engage in kiss-and-run or incomplete fusion. Release probability and timing can be modulated, contributing to short-term plasticity such as facilitation or depression, and to asynchronous or spontaneous miniature release.

Post-release, neurotransmitters diffuse across the synaptic cleft and bind to postsynaptic receptors, which can be ionotropic or metabotropic. This binding generates excitation or inhibition in the postsynaptic cell. Clearance mechanisms include reuptake by presynaptic or glial transporters, vesicular uptake, enzymatic degradation (e.g., acetylcholinesterase for acetylcholine), or diffusion away from the synapse.

Vesicle types and organization support diverse signaling, with small clear synaptic vesicles typically handling fast neurotransmitters and large dense-core vesicles often containing neuropeptides.