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Cell Rep. 2020 Feb 11;30(6):2006-2017.e3. doi: 10.1016/j.celrep.2020.01.051.

Nanoscale Remodeling of Functional Synaptic Vesicle Pools in Hebbian Plasticity.

Author information

1
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom.
2
Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester L1 7RH, United Kingdom.
3
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton BN1 9QG, United Kingdom. Electronic address: k.staras@sussex.ac.uk.

Abstract

Vesicle pool properties are known determinants of synaptic efficacy, but their potential role as modifiable substrates in forms of Hebbian plasticity is still unclear. Here, we investigate this using a nanoscale readout of functionally recycled vesicles in natively wired hippocampal CA3→CA1 circuits undergoing long-term potentiation (LTP). We show that the total recycled vesicle pool is larger after plasticity induction, with the smallest terminals exhibiting the greatest relative expansion. Changes in the spatial organization of vesicles accompany potentiation including a specific increase in the number of recycled vesicles at the active zone, consistent with an ultrastructural remodeling component of synaptic strengthening. The cAMP-PKA pathway activator, forskolin, selectively mimics some features of LTP-driven changes, suggesting that distinct and independent modules of regulation accompany plasticity expression. Our findings provide evidence for a presynaptic locus of LTP encoded in the number and arrangement of functionally recycled vesicles, with relevance for models of long-term plasticity storage.

KEYWORDS:

acute slice; electron microscopy; hippocampus; long-term potentiation; plasticity; presynaptic terminal; recycling pool; synaptic vesicle

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