Abstract
SummaryAt 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.
Highlights
Most information transfer in the CNS depends on fast transmission at chemical synapses, and the mechanisms underlying this process have been extensively examined
Our findings suggest that a small recycling pool supports neurotransmission in native central synapses and that the physical position of recycling vesicles in the terminal is an important factor in their favored stimulus-driven fusion
We combined FM dye labeling with photoconversion and serial electron microscopy to examine the ultrastructural organization of the recycling vesicle pool in small native central synapses
Summary
Most information transfer in the CNS depends on fast transmission at chemical synapses, and the mechanisms underlying this process have been extensively examined. Synaptic vesicles appear morphologically similar, they are, organized into functionally discrete subpools that are key determinants of synaptic performance (Denker and Rizzoli, 2010; Rizzoli and Betz, 2005; Sudhof, 2004). Understanding the specific relationship between these functional pools and their organizational and structural properties is a fundamental issue in neuroscience. What is the absolute size of the functional vesicle pool at a synapse and how does its magnitude relate to other parameters of the synaptic architecture? Do functionally distinct subpools have a specific spatial organization that reflects or supports their operational roles? What molecular substrates regulate this organization and what are the consequences for synaptic function? What is the absolute size of the functional vesicle pool at a synapse and how does its magnitude relate to other parameters of the synaptic architecture? Do functionally distinct subpools have a specific spatial organization that reflects or supports their operational roles? If so, what molecular substrates regulate this organization and what are the consequences for synaptic function?
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