Altered fear engram encoding underlying conditioned versus unconditioned stimulus initiated memory updating

OBJECTIVE It′s known that post-retrieval extinction but not extinction alone could erase fear memory. However, whether the coding pattern of original fear engrams is remodeled or inhibited remains largely unclear. Here we try to investigate whether the coding pattern of memory engrams is altered during post-retrieval extinction induced memory updating. METHODS To answer the question, by using activity-dependent neuronal-tagging technology, neuronal tracing technique combined with optogenetic manipulation and in vivo calcium imaging, we identified the fear and extinction cells in PrL and BLA and investigated the dynamic encoding of memory engram ensembles in the PrL and BLA during CS versus US initiated memory updating.RESULTS We found increased reactivation of engram cells in the prelimbic cortex and basolateral amygdala during memory updating. Moreover, conditioned stimulus and unconditioned stimulu sinitiated memory updating depend on the engram cells reactivation in the prelimbic cortex or basolateral amygdala respectively. Finally,we found memory updating causes increased overlapping between fear and extinction cells and the original fear engrams encoding was altered during memory updating. CONCLUSION Our data provide the first evidence to show the overlapping ensembles between fear and extinction cells and functional reorganization of original engrams underlying conditioned stimulus and unconditioned stimulus initiated memory updating.