title: A preferentially segregated recycling vesicle pool of limited size supports neurotransmission in native central synapses.
abstract: At small central synapses, efficient turnover of vesicles is crucial for stimulus-driven transmission, but how the structure of this recycling pool relates to its functional role remains unclear. Here we characterize the organizational principles of functional vesicles at native hippocampal synapses with nanoscale resolution using fluorescent dye labeling and electron microscopy. We show that the recycling pool broadly scales with the magnitude of the total vesicle pool, but its average size is small (∼45 vesicles), highly variable, and regulated by CDK5/calcineurin activity. Spatial analysis demonstrates that recycling vesicles are preferentially arranged near the active zone and this segregation is abolished by actin stabilization, slowing the rate of activity-driven exocytosis. Our approach reveals a similarly biased recycling pool distribution at synapses in visual cortex activated by sensory stimulation in vivo. We suggest that in small native central synapses, efficient release of a limited pool of vesicles relies on their favored spatial positioning within the terminal.
authors.affiliation: School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Marra
authors.forename: Jemima J
authors.initials: JJ
authors.lastname: Burden
authors.forename: Julian R
authors.initials: JR
authors.lastname: Thorpe
authors.forename: Ikuko T
authors.initials: IT
authors.lastname: Smith
authors.forename: Spencer L
authors.initials: SL
authors.lastname: Smith
authors.forename: Michael
authors.initials: M
authors.lastname: Häusser
authors.forename: Tiago
authors.initials: T
authors.lastname: Branco
authors.forename: Kevin
authors.initials: K
authors.lastname: Staras
mesh_terms: D000818:Animals; D004705:Endocytosis / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure