Two forms of asynchronous release with distinctive spatiotemporal dynamics in central synapses

• Published in: eLife Vol. 12
• Main Authors: Malagon, Gerardo, Myeong, Jongyun, Klyachko, Vitaly A
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 11.05.2023; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Action potential; Action Potentials; active zone; Analysis; Animals; Asynchronous communications; asynchronous release; Calcium; Calcium, Dietary; Endocytosis; Hippocampus; Localization; Methods; Neuroscience; Neurotransmitter Agents; Neurotransmitter release; presynaptic organization; Rats; Spatial analysis (Statistics); Subpopulations; Synapses; synaptic terminals; Synaptic Transmission - physiology; United States; presynaptic organization; rat; neuroscience; active zone; neurotransmitter release; asynchronous release; synaptic terminals
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.84041

Asynchronous release is a ubiquitous form of neurotransmitter release that persists for tens to hundreds of milliseconds after an action potential. How asynchronous release is organized and regulated at the synaptic active zone (AZ) remains debatable. Using nanoscale-precision imaging of individual release events in rat hippocampal synapses, we observed two spatially distinct subpopulations of asynchronous events, ~75% of which occurred inside the AZ and with a bias towards the AZ center, while ~25% occurred outside of the functionally defined AZ, that is, ectopically. The two asynchronous event subpopulations also differed from each other in temporal properties, with ectopic events occurring at significantly longer time intervals from synchronous events than the asynchronous events inside the AZ. Both forms of asynchronous release did not, to a large extent, utilize the same release sites as synchronous events. The two asynchronous event subpopulations also differ from synchronous events in some aspects of exo-endocytosis coupling, particularly in the contribution from the fast calcium-dependent endocytosis. These results identify two subpopulations of asynchronous release events with distinctive organization and spatiotemporal dynamics.