presynapse

Presynapse refers to the specialized region of a neuron that initiates communication with another neuron or a target cell. At chemical synapses, the presynaptic side is typically organized around the presynaptic terminal or bouton, which contains synaptic vesicles, voltage-gated calcium channels, and a protein-rich active zone that governs neurotransmitter release. The presynaptic terminal also houses mitochondria and cytoskeletal elements that support vesicle trafficking and membrane turnover.

The core function of the presynapse is to release neurotransmitters in response to an action potential. When the action potential arrives, it depolarizes the presynaptic membrane and opens voltage-gated calcium channels, allowing calcium ions to enter. The rise in intracellular calcium triggers fusion of synaptic vesicles with the presynaptic membrane via the SNARE protein complex. Vesicle-associated v-SNAREs (such as synaptobrevin/VAMP) interact with target membrane t-SNAREs (syntaxin-1 and SNAP-25), with the calcium sensor synaptotagmin guiding the fusion process. After fusion, neurotransmitters are released into the synaptic cleft, diffuse across the gap, and bind to receptors on the postsynaptic cell, producing excitatory or inhibitory responses.

Following release, vesicle components are recycled through endocytosis to form new vesicles. This recycling process often involves clathrin-mediated pathways and can include Kiss-and-Run mechanisms. Vesicles are then refilled with neurotransmitter and re-enter various vesicle pools, such as readily releasable, recycling, or reserve pools, to regulate release probability and short-term plasticity.

Presynaptic function is influenced by the type and amount of neurotransmitter released, the organization of the active zone, and a network of accessory proteins that fine-tune release. Dysfunctions in presynaptic mechanisms are associated with several neurological disorders and contribute to broader synaptic pathophysiology.