Vesicles derived via AP-3-dependent recycling contribute to asynchronous release and influence information transfer

• Type of Material: Article
• Authors: Alesya Evstratova, Laval University; Simon Chamberland, Laval University; Victor Faundez, Emory University; Katalin Toth, Laval University
• Language: English
• Date: 2014-11-01
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Macmillan Publishers Limited. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms6530
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 5
• Start Page: 5530
• End Page: 5530
• Grant/Funding Information: This work was supported by CIHR Operating grant to K.T. (MOP-81142) and grants from the National Institutes of Health (GM077569 and NS42599) and CHOA Children’s Center for Neuroscience to VF.; A.E was supported by CTRN fellowship and S.C. was supported by NSERC and CTRN scholarships.
• Keywords: GRANULE CELLS; MOSSY-FIBER SYNAPSES; NETWORK ACTIVITY; Science & Technology - Other Topics; Science & Technology; SYNAPTIC VESICLES; GABA RELEASE; CA2+ SENSOR; Multidisciplinary Sciences; TRANSMITTER RELEASE; SHORT-TERM PLASTICITY; GENETIC-ANALYSIS; SPONTANEOUS NEUROTRANSMITTER RELEASE
• Research Categories: Biology, Neuroscience; Biology, Cell

Abstract

Action potentials trigger synchronous and asynchronous neurotransmitter release. Temporal properties of both types of release could be altered in an activity-dependent manner. While the effects of activity-dependent changes in synchronous release on postsynaptic signal integration have been studied, the contribution of asynchronous release to information transfer during natural stimulus patterns is unknown. Here we find that during trains of stimulations, asynchronous release contributes to the precision of action potential firing. Our data show that this form of release is selectively diminished in AP-3b2 KO animals, which lack functional neuronal AP-3, an adaptor protein regulating vesicle formation from endosomes generated during bulk endocytosis. We find that in the absence of neuronal AP-3, asynchronous release is attenuated and the activity-dependent increase in the precision of action potential timing is compromised. Lack of asynchronous release decreases the capacity of synaptic information transfer and renders synaptic communication less reliable in response to natural stimulus patterns.