title: Control of Spike Transfer at Hippocampal Mossy Fiber Synapses In Vivo by GABAA and GABAB Receptor-Mediated Inhibition.
abstract: 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 GABAAreceptors was responsible for the direct inhibition of light-evoked spike responses, the slow inhibition of spiking activity required the activation of GABABreceptors 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.
  
  
  
  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 GABAAand GABABreceptors to control the efficacy and temporal rules for information transfer at DG-CA3 connections.
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Stefano
authors.identifier: 0000-0002-8781-3295
authors.initials: S
authors.lastname: Zucca
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Marilena
authors.identifier: 0000-0003-4067-8927
authors.initials: M
authors.lastname: Griguoli
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Meryl
authors.identifier: 0000-0001-9669-0154
authors.initials: M
authors.lastname: Malézieux
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Grosjean
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France.
authors.forename: Mario
authors.identifier: 0000-0003-1225-2742
authors.initials: M
authors.lastname: Carta
authors.affiliation: Interdisciplinary Institute for Neuroscience, CNRS, Unité Mixte de Recherche 5297, University of Bordeaux, F-33000 Bordeaux, France christophe.mulle@u-bordeaux.fr.
authors.forename: Christophe
authors.identifier: 0000-0003-2709-6615
authors.initials: C
authors.lastname: Mulle
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
chemical_list: D018756:GABA Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B
keywords: CA3; dentate gyrus; feedforward inhibition; hippocampus; in vivo; synapse