Hippocampal Remapping after Partial Inactivation of the Medial Entorhinal Cortex

Hippocampal place cells undergo remapping when the environment is changed. The mechanism of hippocampal remapping remains elusive but spatially modulated cells in the medial entorhinal cortex (MEC) have been identified as a possible contributor. Using pharmacogenetic and optogenetic approaches, we tested the role of MEC cells by examining in mice whether partial inactivation in MEC shifts hippocampal activity to a different subset of place cells with different receptive fields. The pharmacologically selective designer Gi-protein-coupled muscarinic receptor hM4D or the light-responsive microbial proton pump archaerhodopsin (ArchT) was expressed in MEC, and place cells were recorded after application of the inert ligand clozapine-N-oxide (CNO) or light at appropriate wavelengths. CNO or light caused partial inactivation of the MEC. The inactivation was followed by substantial remapping in the hippocampus, without disruption of the spatial firing properties of individual neurons. The results point to MEC input as an element of the mechanism for remapping in place cells.