200. Synaptic Vesicle Cycle

Synaptic Vesicle Cycle

This simulation models the complete life cycle of synaptic vesicles at the presynaptic terminal, from docking through neurotransmitter release and membrane recycling. The cycle is fundamental to all chemical synaptic transmission.

SNARE-Mediated Fusion

• v-SNAREs: Synaptobrevin-2 on vesicle membrane
• t-SNAREs: Syntaxin-1 and SNAP-25 on plasma membrane
• Zippering: SNARE complex assembly drives membrane fusion

The Cycle Stages

• Docking: Physical attachment of vesicles to active zone via Munc-18 and RIM
• Priming: Munc-13 opens syntaxin conformation, SNARE complex partially assembles
• Calcium Sensing: Synaptotagmin-1 (Syt1) binds Ca²⁺, triggers membrane merger
• Fusion: Full SNARE zippering, pore formation, neurotransmitter release
• Endocytosis: Membrane retrieval via clathrin-mediated or ultrafast endocytosis
• Refilling: Vesicle re-acidification and neurotransmitter loading

Vesicle Pools

• Reserve Pool: ~80% of vesicles, mobilized only during intense stimulation
• Recycling Pool: ~15% of vesicles, sustain transmission during moderate activity
• Readily Releasable Pool (RRP): ~5% of vesicles, docked and primed for immediate release

Recycling Modes

• Kiss-and-Run: Brief fusion pore opening, rapid closure, fastest recycling
• Clathrin-Mediated: Full collapse, coat assembly, scission by dynamin
• Ultrafast Endocytosis (UFE): 50-100ms retrieval of large membrane patches
• Activity-Dependent Bulk Endocytosis: Large endosome formation during intense activity

SNARE Recycling

After fusion, NSF (N-ethylmaleimide-sensitive factor) uses ATP hydrolysis to disassemble cis-SNARE complexes on the plasma membrane, allowing synaptobrevin to be endocytosed and repackaged into new vesicles.