BMI Progress Reports 2021 // Prof. Gräff's Lab: L. Dixsaut "Where does the engram come from? Study of prefrontal cortical inputs during memory consolidation"

The formation and storage of memories has been under deep investigation for several decades. Nevertheless, the precise mechanisms by which memories are initially encoded and subsequently stored in different brain areas are still unknown. However, we can theoretically define cells carrying a memory as engram cells that are activated at the time of learning, that undergo enduring molecular modifications after learning, that are reactivated upon recall of the memory and which reactivation drives the recall itself. Recent evidence has suggested that the medial prefrontal cortex (mPFC) contains engram cells already at encoding, but in contrast to hippocampal engram cells, mPFC engram cells are kept silent during the recall until the memory is fully consolidated. These findings stipulate that inputs to the mPFC are differentially activated over the course of memory consolidation.
In order to identify the activation patterns of specific cortical projections, we screened the activity of mPFC inputs throughout consolidation of a fear memory using an unbiased retrograde tracing in adult mice. We further tested their functional relevance by chemogenetically inhibiting these projections during the different learning phases. This highlighted the role of Claustrum and Basolateral Amygdala inputs to the mPFC during the encoding of the fear memory, as well as the surprising influence of the Insular cortex input at recent recall. This indicates that there might be a switch occurring in the mPFC inputs during consolidation.  Finally, we investigated the effect of those manipulations on the reactivation of the original mPFC engram using the engram tagging cFos-tTA mouse line.
Collectively, our data help to further refine the working model of memory formation by deciphering the interplay between brain regions during the process of systems consolidation of a fear memory.