Venue: Neurocentre Magendie – conference room
Defense in english
Pierre Feugas
Herry’s team (Neurocentre Magendie)
Thesiss supervisor: Cyril Dejean
Title
Role of hippocampo-prefrontal circuits in fear memory consolidation
Abstract
Following a pavlovian fear conditioning (FC) task, mice learn to associate a sound with an electric shock. Concurrent with this learning we observed a subset of neurons in the dorso-medial prefrontal cortex (dmPFC) that show synchronous activation on the ascending phase of 4Hz oscillations during fear expression, we named them “assembly neurons” (AN). We hypothesize that this synchronous activation is the cortical representation of the consolidated associative memory. The ventral part of the hippocampus (vHPC) appears as a likely candidate to orchestrate this memory consolidation. Systems consolidation theory posits that memory formation starts in the hippocampus before being transferred to cortical regions for long term retention. The ventral region is specifically implicated in emotional memory and a monosynaptic connection exists between its CA1 field and the PFC. The CA1-field of the vHPC is also the source of high frequency sleep oscillations called Sharp-wave-ripples. These events could act as the supporting mechanism for consolidation, synchronously activating neurons in downstream regions and strengthening their synaptic weights.To test this hypothesis we used in vivo extracellular electrophysiological recordings of single-units and large-field potentials in the PFC and vHPC during sleep and awake behavior. We found that PFC neurons participating in the memory trace display increasing and specific co-activity around sharp-wave ripples (SWRs) throughout post-conditioning sleep, thus highlighting the role of Sharp wave ripples in the consolidation of fear memory. To investigate the causal role of ripples on fear memory consolidation we used optogenetics to inhibit the pathway from vHPC to PFC during ripples using a closed-loop system. We designed and tested the efficiency of a closed-loop system using measures of performances until we obtained results satisfying our conditions of stimulation.
Inhibiting the vHPC-dmPFC pathway during post-conditioning sleep induced a decrease of freezing behavior compared to control animals, indicating the role of this pathway and SWRs in fear memory consolidation.
Keywords: Fear, Memory, Prefrontal Cortex, Hippocampus, Consolidation, Circuits
Jury
Dr. HUMEAU, Yann Directeur de recherche, IINS Centre Broca Président-Examinateur
Dr. WIENER, Sidney Directeur de recherche émérite, Collège de France Rapporteur
Dre. DOYERE, Valérie Directrice de recherche, NeuroPSI-UMR9197 Rapporteur
Dr. LEBLOIS, Arthur Chargé de recherche, IMN Centre Broca Examinateur
Dre. LE MOINE, Catherine Directrice de recherche, INCIA Bordeaux Membre Invité