The readily-releasable pool dynamically regulates multivesicular release

The number of neurotransmitter-filled vesicles released into the synaptic cleft with each action potential dictates the reliability of synaptic transmission. Variability of this fundamental property provides diversity of synaptic function across brain regions, but the source of this variability is u...

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Bibliographic Details
Published in:eLife 2019-07, Vol.8
Main Authors: Vaden, Jada H, Banumurthy, Gokulakrishna, Gusarevich, Eugeny S, Overstreet-Wadiche, Linda, Wadiche, Jacques I
Format: Article
Language:English
Subjects:
Action potential
Alzheimer's disease
Animals
Autism
Brain
Brain slice preparation
Calcium
Calcium - metabolism
Calcium Signaling
cerebellum
Containers
Cyclic AMP-Dependent Protein Kinases - metabolism
Enzymes
Kinases
Mice
Models, Biological
Molecular modelling
Neurons
Neuroscience
Neurosciences
Neurotransmitters
Occupancy
Physiological aspects
Protein kinase A
Protein kinases
RRP
Synapsin
Synapsins - metabolism
Synaptic cleft
Synaptic Transmission
Synaptic vesicles
Synaptic Vesicles - metabolism
vesicle release
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Description
Summary:The number of neurotransmitter-filled vesicles released into the synaptic cleft with each action potential dictates the reliability of synaptic transmission. Variability of this fundamental property provides diversity of synaptic function across brain regions, but the source of this variability is unclear. The prevailing view is that release of a single (univesicular release, UVR) or multiple vesicles (multivesicular release, MVR) reflects variability in vesicle release probability, a notion that is well-supported by the calcium-dependence of release mode. However, using mouse brain slices, we now demonstrate that the number of vesicles released is regulated by the size of the readily-releasable pool, upstream of vesicle release probability. Our results point to a model wherein protein kinase A and its vesicle-associated target, synapsin, dynamically control release site occupancy to dictate the number of vesicles released without altering release probability. Together these findings define molecular mechanisms that control MVR and functional diversity of synaptic signaling.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.47434