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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.

Distinctions between cell types underpin organizational principles for nervous system function. Functional variation also exists between neurons of the same type. This is exemplified by correspondence between grid cell spatial scales and the synaptic integrative properties of stellate cells (SCs) in the medial entorhinal cortex. However, we know little about how functional variability is structured either within or between individuals. Using ex-vivo patch-clamp recordings from up to 55 SCs per mouse, we found that integrative properties vary between mice and, in contrast to the modularity of grid cell spatial scales, have a continuous dorsoventral organization. Our results constrain mechanisms for modular grid firing and provide evidence for inter-animal phenotypic variability among neurons of the same type. We suggest that neuron type properties are tuned to circuit-level set points that vary within and between animals.