Telencephalic outputs from the medial entorhinal cortex are copied directly to the hippocampus

Abstract

Complementary actions of the neocortex and the hippocampus enable encoding and long-term storage of experience dependent memories. Standard models for memory storage assume that sensory signals reach the hippocampus from superficial layers of the entorhinal cortex (EC). Deep layers of the EC on the other hand relay hippocampal outputs to the telencephalic structures including many parts of the neocortex. Here we show that cells in Layer 5a of the medial EC send a copy of their telencephalic outputs back to the CA1 region of the hippocampus. Combining cell-type specific anatomical tracing, high-throughput RNA-sequencing based projection mapping and optogenetics aided circuit mapping, we show that these projections have a unique topography and target hippocampal pyramidal cells and interneurons. Our results suggest that rather than serving as a relay, deep EC may coordinate hippocampal-neocortical interactions in spatial cognition and memory.