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

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 with high-throughput RNA-sequencing based projection mapping and optogenetics aided circuit mapping, we show that in the mouse brain these projections have a unique topography and target hippocampal pyramidal cells and interneurons. Our results suggest that projections of deep medial EC neurons are anatomically configured to influence the hippocampus and neocortex simultaneously and therefore lead to novel hypotheses on the functional role of the deep EC.

Automated summary

Complementary actions of the neocortex and the hippocampus facilitate the encoding and storage of experience dependent memories. This study reveals that deep layer neurons in the medial entorhinal cortex project to both the hippocampus and neocortex, suggesting a simultaneous influence on these two brain regions.