LAUSR

Significance Retrosplenial cortex (RSC) is a major relay of hippocampal formation output to other neocortical areas and is critical for spatial and some other forms of learning. We show here that the sparse, orthogonal, “place cell” sequence activity in RSC develops gradually over several days and is severely attenuated by hippocampal damage. These data support the theory that hippocampus endows RSC (and possibly other cortical areas) with an index-like, continuous representation of the context in which events occur, that could support coordinated retrieval of recent memory. Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex.