Control of Spike Transfer at Hippocampal Mossy Fiber Synapses In Vivo by GABA A and GABA B Receptor-Mediated Inhibition

Stefano Zucca, Marilena Griguoli, Meryl Malézieux, Noëlle Grosjean, Mario Carta, Christophe Mulle
J. Neurosci.. 2016-12-02; 37(3): 587-598
DOI: 10.1523/JNEUROSCI.2057-16.2016

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Zucca S(1), Griguoli M(1), Malézieux M(1), Grosjean N(1), Carta M(1), Mulle C(2).

Author information:
(1)Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
(2)Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France

Despite extensive studies in hippocampal slices and incentive from computational
theories, the synaptic mechanisms underlying information transfer at mossy fiber
(mf) connections between the dentate gyrus (DG) and CA3 neurons in vivo are
still elusive. Here we used an optogenetic approach in mice to selectively
target and control the activity of DG granule cells (GCs) while performing
whole-cell and juxtacellular recordings of CA3 neurons in vivo In CA3 pyramidal
cells (PCs), mf-CA3 synaptic responses consisted predominantly of an IPSP at low
stimulation frequency (0.05 Hz). Upon increasing the frequency of stimulation, a
biphasic response was observed consisting of a brief mf EPSP followed by an
inhibitory response lasting on the order of 100 ms. Spike transfer at DG-CA3
interneurons recorded in the juxtacellular mode was efficient at low presynaptic
stimulation frequency and appeared insensitive to an increased frequency of GC
activity. Overall, this resulted in a robust and slow feedforward inhibition of
spike transfer at mf-CA3 pyramidal cell synapses. Short-term plasticity of EPSPs
with increasing frequency of presynaptic activity allowed inhibition to be
overcome to reach spike discharge in CA3 PCs. Whereas the activation of GABAA
receptors was responsible for the direct inhibition of light-evoked spike
responses, the slow inhibition of spiking activity required the activation of
GABAB receptors in CA3 PCs. The slow inhibitory response defined an optimum
frequency of presynaptic activity for spike transfer at ∼10 Hz. Altogether these
properties define the temporal rules for efficient information transfer at
DG-CA3 synaptic connections in the intact circuit.
SIGNIFICANCE STATEMENT: Activity-dependent changes in synaptic strength
constitute a basic mechanism for memory. Synapses from the dentate gyrus (DG) to
the CA3 area of the hippocampus are distinctive for their prominent short-term
plasticity, as studied in slices. Plasticity of DG-CA3 connections may assist in
the encoding of precise memory in the CA3 network. Here we characterize DG-CA3
synaptic transmission in vivo using targeted optogenetic activation of DG
granule cells while recording in whole-cell patch-clamp and juxtacellular
configuration from CA3 pyramidal cells and interneurons. We show that, in vivo,
short-term plasticity of excitatory inputs to CA3 pyramidal cells combines with
robust feedforward inhibition mediated by both GABAA and GABAB receptors to
control the efficacy and temporal rules for information transfer at DG-CA3

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