Optogenetic Dissection of Entorhinal-Hippocampal Space Circuit

Abstract

Spatial representation system of brain is comprised of place cells located in the hippocampus and grid cells, head-direction cells, and border cells found in the medial entorhinal cortex. There is a prominent circuitry between the hippocampus and the medial entorhinal cortex; however, exactly which entorhinal functional cell types project to hippocampus has not been determined yet. By injecting retrogradely transportable recombinant adeno-associated virus carrying channelrhodopsin-2 transgene in the hippocampus, optogenetic control over entorhinal neurons with direct projections to the hippocampus has been introduced. Using optogenetics together with electrophysiological recordings in vivo we were able to identify functionally defined hippocampus projecting entorhinal neurons as cell that responded with minimal latency to laser stimulations in the medial entorhinal cortex. A substantial portion of responsive cells were grid cells, but we also found other directionally or spatially modulated responsive cells, like head-direction and border cells, as well as principal unknown cells and interneurons. Our findings indicate that neural code transformation within the hippocampal-entorhinal circuit and generation of place fields may be achieved by combining broad spectrum of functionally defined inputs arising from medial entorhinal cortex.