Hippocampal-medial entorhinal circuit is differently organized along the dorsoventral axis in rodents

The general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projection to the medial EC (MEC). Whereas dorsal hippocampal projections are confined to the dorsal MEC and preferentially target layer Vb (LVb) over layer Va (LVa) neurons, the ventral hippocampus innervates the entire dorsoventral extent of MEC. In the ventral MEC, these projections innervate neurons in both LVa and LVb. In contrast, in the dorsal MEC, ventral hippocampal projections target mainly LVa neurons. As LVa neurons project to telencephalic structures, our findings indicate that the ventral hippocampus regulates LVa-mediated entorhinal-neocortical output from both the dorsal and ventral MEC. Overall, the marked dorsoventral differences in hippocampal-entorhinal connectivity impose important constraints on signal flow in hippocampal-neocortical circuits.