ROLE OF HIPPOCAMPO-PREFRONTAL CIRCUITS IN FEAR MEMORY CONSOLIDATION

Fear disorders are among the most frequent psychiatric conditions. We previously showed that assembly neurons (AN), a subset of prefrontal cortex (PFC) neurons, synchronize during fear expression. We hypothesize that this synchronous activation is the cortical representation of consolidated associative memory. We can model fear in mice through auditory Pavlovian fear conditioning (FC) which allows us to study the mechanisms underlying fear memory consolidation and the synchronization of neuronal activity observed during fear expression. It is known that sharp wave ripples (SWRs), which are transient oscillatory events in the hippocampus (HPC), play a crucial role in memory consolidation. SWRs are essential for transferring and storing information from HPC to PFC. Therefore, we are investigating how SWR and excitatory HPC-PFC projections contribute to memory consolidation and synchronization of AN. For this, we are using in vivo electrophysiology to record HPC and PFC activities during FC in mice. It enables us to detect SWR events and examine PFC neuronal activity during these events. We can identify AN during the retrieval phase of FC and track their activity throughout the entire behavioral paradigm. We showed that PFC neurons participating in the memory trace display increasing and specific co-activity around SWRs following FC. Furthermore, we used real-time closed-loop optogenetic stimulation to inhibit HPC-PFC projections during SWR detection in the consolidation phase of FC. Preliminary results suggest that inhibition of vHPC-PFC projections during SWRs leads to a decrease in fear memory expression, highlighting the fundamental role of SWRs and HPC-PFC circuits in fear memory consolidation.