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Proc Natl Acad Sci U S A. 2018 Jul 10;115(28):7434-7439. doi: 10.1073/pnas.1720659115. Epub 2018 Jun 26.

Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus.

Author information

1
Department of Psychiatry and Neuroscience, CERVO Brain Research Centre, Université Laval, Quebec City, QC G1J 2G3, Canada.
2
Department of Computer Science, University of Warwick, Coventry, United Kingdom.
3
Centre for Complexity Science, University of Warwick, Coventry CV4 7AL, United Kingdom.
4
University College London Institute of Neurology, University College London, London WC1E 6BT, United Kingdom.
5
University College London Institute of Neurology, University College London, London WC1E 6BT, United Kingdom k.volynski@ucl.ac.uk katalin.toth@fmed.ulaval.ca.
6
Department of Psychiatry and Neuroscience, CERVO Brain Research Centre, Université Laval, Quebec City, QC G1J 2G3, Canada; k.volynski@ucl.ac.uk katalin.toth@fmed.ulaval.ca.

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 Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays constant during action potential trains and that accumulated residual Ca2+ is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+ dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+ buffers calbindin-D28K and calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+ channels and release sensors and the relatively slow Ca2+ extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.

KEYWORDS:

hippocampus; mossy fiber; presynaptic release; short-term plasticity

PMID:
29946034
PMCID:
PMC6048548
DOI:
10.1073/pnas.1720659115
[Indexed for MEDLINE]
Free PMC Article

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