Role of retrosplenial cortex in memory

Memories are an enduring record of our past experiences that form the essence of our affect, our socio-cognitive functioning, and, to a great extent, our very identity. The biological importance of the ability to learn and to memorize is highlighted by the fact that processes such as synaptic plasticity a proposed cellular correlate of learning- are highly evolutionarily conserved among a wide range of species, from flies to humans. Moreover, in many cases the very same biological, chemical and biophysical laws, as well as the genes and molecules implicated, are preserved across the long chain of evolution. However, despite considerable advances of modern neuroscience, much remains unknown about the brain mechanisms of long-term memory storage.. One of the most important contributions to this question came from the seminal work of Brenda Milner, William Scoville and Wilder Penfield, who identified the hippocampus as an important structure required for spatial learning and memory processes. Later studies would further reveal that learning and memory are not anatomically and functionally adscript to a single brain region, and that other areas most notably the neocortex, contribute to memory storage. One of the most prominent theories of memory formation and storage, the systems consolidation theory, proposes that while recently acquired memories are hippocampus-dependent, as time passes by, cortical mechanisms gradually take over. Despite this view, there is increasing evidence that posterior cortices, including the retrosplenial cortex, seem to play persistent, time-unlimited roles in memory formation and retrieval. The retrosplenial cortex has indeed many connections with the hippocampal formation and neocortex, and can thus convey signals between these areas relevant for memory storage. Accordingly, recent evidence shows that the retrosplenial cortex plays an important role in the processing of episodic memories in animal models. Building on this work, the goal of the current project is to advance our understanding on the cellular mechanisms by which the retrosplenial cortex supports persistent memory storage and relays information to other cortical areas. Using molecular biological, behavioral, electrophysiological and imaging assays, in combination with cell-specific chemogenetic manipulations, this project aims to identify the retrosplenial cortical neurons which play key roles in the processing of lasting memories. The relevant neuronal populations could be potential targets for treatment of memory disorders.