Memory encoding by cortical circuits and engrams

From the moment that humans became aware that our collection of memories defines who we are, many efforts have been made to better understand how memories are acquired, stored and retrieved. This may be with the goal to precisely describe how new memories are formed and retained or with the goal to change/erase memories that have already been formed. Both perspectives might prove crucial for a proper understanding of aberrant behavior, as is the case with substance abuse disorder or Post Traumatic Stress Disorder. The medial prefrontal cortex (mPFC) is considered an important hub for normal and aberrant memory processing and therefore I aimed in this thesis to identify memory-encoding neurons in the mPFC and to disentangle intrinsic mPFC circuits that support memory expression and extinction. With this research, I provide novel insights into the role of mPFC neurons and circuitry in memory processing. While these findings improve and detail our understanding of memory consolidation and extinction learning, they also open new avenues of research. Firstly, my data stresses the relevance of how conditioning strength shapes neuronal ensembles and the brain-wide neuronal circuit that supports remote memory expression. Secondly, I revealed a novel internal mPFC circuit that controls extinction learning through interaction between the ventral and dorsal mPFC (vmPFC and dmPFC). These results challenge the assignment of a simple stop and go function to the vmPFC and dmPFC, respectively. Furthermore, I also implicate the role of a specific GABAergic interneuron population in memory extinction and how it mediates the interplay between the dorsal and ventral areas of the mPFC. Taken together, my thesis reinforces the necessity of combining the local and interregional identification of behaviorally-specific neuronal ensembles and neuronal circuitry supporting memory encoding, consolidation, retrieval and extinction, with the ultimate goal to develop better treatment options for debilitating memory disorders.