• Catherine Marneffe, Ana Moreira-de-Sá, Simon Lecomte, Anaël Erhardt, and Christophe Mulle.
• Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, France; University of Bordeaux, F-33000 Bordeaux, France.
• Neuroscience. 2024 Sep 26.

AbstractShort-term synaptic plasticity refers to the regulation of synapses by their past activity on time scales of milliseconds to minutes. Hippocampal mossy fiber synapses onto CA3 pyramidal cells (Mf-CA3 synapses) are endowed with remarkable forms of short-term synaptic plasticity expressed as facilitation of synaptic release by a factor of up to ten-fold. Three main forms of short-term plasticity are distinguished: 1) Frequency facilitation, which includes low frequency facilitation and train facilitation, operating in the range of tens of milliseconds to several seconds; 2) Post-tetanic potentiation triggered by trains of high frequency stimulation, which lasts several minutes; 3) Finally, depolarization-induced potentiation of excitation, based on retrograde signaling, with an onset and offset of several minutes. Here we describe the proposed mechanisms for short-term plasticity, mainly based on the kinetics of presynaptic Ca2+ transients and the Ca2+ sensor synaptotagmin 7, on cAMP-dependent mechanisms and readily releasable vesicle pool, and on the regulation of presynaptic K+ channels. We then review evidence for a physiological function of short-term plasticity of Mf-CA3 synapses in information transfer between the dentate gyrus and CA3 in conditions of natural spiking, and discuss how short-term plasticity counteracts robust feedforward inhibition in a frequency-dependent manner. Although DG-CA3 connections have long been proposed to play a role in memory, direct evidence for an implication of short-term plasticity at Mf-CA3 synapses is mostly lacking. The mechanistic knowledge gained on short-term plasticity at Mf-CA3 synapses should help in designing future experiments to directly test how this evolutionary conserved feature controls hippocampal circuit function in behavioural conditions.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

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