Abstract

The retrosplenial cortex (RSC) is a key brain area supporting spatial memory and navigation. It receives strong inputs from the hippocampal complex (parahippocampal region, subiculum) as well as visual cortical areas. In a pilot study, we demonstrated for the first time spatial memory engrams in mouse dysgranular RSC (Rdg) in the form of specific patterns of activity. Their stability is correlated with the degree of spatial memory retention. We also found robust visual responses in Rdg which were strongly modulated by locomotion. Our initial study did not tell us what those engrams represent: the environment, rewarded locations in the environment, or the animal’s movement and navigation within the environment. It also did not tell us whether engrams depend on hippocampal or visual inputs for their formation, and how these inputs interact in Rdg over time during memory acquisition. We will address these questions using calcium imaging in mice that will either (1) be implanted with a miniscope and will be freely moving in a radial arm maze, or (2) will be trained in a virtual corridor and imaged head-fixed using a standard two-photon microscope. We will manipulate intra- and extra-maze visual cues, spatial parameters of the maze as well as reward magnitudes. We will use DREADDs to inactivate specific populations of neurons in visual areas of the dorsal stream or the dorsal hippocampus, both of which form functional networks with Rdg. We will further test the role of Rdg engrams in cross-modal object memory by successively removing visual cues or placing mice in the dark at different points during memory acquisition or testing. Finally, we will investigate the direction of information flow between Rdg, hippocampus and the visual cortex, and how this develops over time during of the acquisition and retrieval of spatial memory. This will be achieved through recordings of local field potentials in the 3 areas at the same time, and Granger causality analysis.