Abstract

Current models of spatial cognition and memory assume that the medial and lateral entorhinal cortex (MEC/LEC) send parallel streams of information to the hippocampus. However, anatomical and functional studies suggest that MEC and LEC may also interact directly, but how these interactions are organised and what their functional consequences are has received little attention. Our preliminary data shows that fan cells in layer 2 of LEC send direct projections to principal neurons and interneurons in layers 1 and 2 of MEC. Fan cells are known to be critical for episodic-like memory and manifest early pathology in Alzheimer’s Disease. Here, we propose to determine when and how fan cell projections influence neural representations in the MEC using chemogenetic, optogenetic and imaging tools in combination with electrophysiology and behaviour. We will use ex-vivo approaches to delineate roles of local inhibitory networks in complex responses of MEC principal cells to activation of fan cell inputs. We will determine when fan cell projections to MEC are active during behaviour and what their effect is on functionally identified neurons. Finally, we will test the contribution of fan cell projections to functional representations and evaluate roles of local inhibitory circuits. By delineating circuit mechanisms for functional interactions between two key brain areas our results will motivate new systems models for spatial cognition and memory. Further, they will establish candidate circuit mechanisms for symptoms of Alzheimer’s Disease, such as wandering behaviour and episodic memory impairment, which could arise from degradation of LEC-MEC interactions.