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TitleAction potential counting at giant mossy fiber terminals gates information transfer in the hippocampus.
Publication TypeJournal Article
Year of Publication2018
AuthorsChamberland, Simon, Yulia Timofeeva, Alesya Evstratova, Kirill Volynski, and Katalin Toth
JournalProc Natl Acad Sci U S A
Volume115
Issue28
Pagination7434-7439
Date Published2018 07 10
ISSN1091-6490
KeywordsAction Potentials, Animals, CA3 Region, Hippocampal, Calcium, Calcium Signaling, Male, Models, Neurological, Mossy Fibers, Hippocampal, Presynaptic Terminals, Pyramidal Cells, Rats
Abstract

Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca imaging we also show that the magnitude of evoked Ca influx stays constant during action potential trains and that accumulated residual Ca is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca influx, buffering, and diffusion, and a Monte Carlo model of Ca-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca buffers calbindin-D and calmodulin and by the loose coupling between presynaptic voltage-gated Ca channels and release sensors and the relatively slow Ca extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.

DOI10.1073/pnas.1720659115
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29946034
PubMed Central IDPMC6048548
Grant List / / Wellcome Trust / United Kingdom
MR/M013812/1 / / Medical Research Council / United Kingdom
MOP-81142 / / CIHR / Canada