Involvement of entorhinal input to the hippocampus in processing “what” and “where” information in twin variants of a memory task

Episodic memory (EM), the remembrance of an event with spatiotemporal (what-where-when) information relies on the hippocampus (HP) and the entorhinal cortex (EC). The superficial layers of the EC provide the primary input to the HP via the perforant path, so we use a mouse line capable of expressing chemogenetic inhibitors in a particular set of projection neurons of EC Layer II (EC stellate and fan cells) to examine the precise role played by EC inputs in different forms of episodic memory. For this we employ an episodic memory task with both olfactory and spatial twin variants. Both are identical except for the feature associated with the reward, animals must dig for rewards while four odors randomly move between bait cups. Essentially, in the olfactory variant animals must mind a particular odor (i.e. the “what” group) and ignore the cup location to obtain the reward, while the other requires the converse (i.e. the “where” group). Mice readily learn both forms of the task, although the spatial variant takes more time. We can thereby assess how the inactivation of the main input neurons to the HP affects behavioral output at different time-points in each variant of the task. We also use calcium imaging to investigate how the changes in CA1 activity correlate with behavioral performance in the two kinds of tasks, both with the intact or silenced EC input. This will increase our understanding of how distinct kinds of EM are processed by the hippocampal/entorhinal circuit.