A direct lateral entorhinal cortex to hippocampal CA2 circuit conveys social information required for social memory

The precise functional role of the hippocampus remains a topic of much debate. The dominant view is that the dorsal (or posterior) hippocampus is implicated in memory and spatial navigation and the ventral (or anterior) hippocampus mediates anxiety-related behaviours. However, this 'dichotomy view' may need revision. Gene expression studies demonstrate multiple functional domains along the hippocampal long axis, which often exhibit sharply demarcated borders. By contrast, anatomical studies and electrophysiological recordings in rodents suggest that the long axis is organized along a gradient. Together, these observations suggest a model in which functional long-axis gradients are superimposed on discrete functional domains. This model provides a potential framework to explain and test the multiple functions ascribed to the hippocampus.

Forming distinct representations of multiple contexts, places, and episodes is a crucial function of the hippocampus. The dentate gyrus subregion has been suggested to fulfill this role. We have tested this hypothesis by generating and analyzing a mouse strain that lacks the gene encoding the essential subunit of the N-methyl-d-aspartate (NMDA) receptor NR1, specifically in dentate gyrus granule cells. The mutant mice performed normally in contextual fear conditioning, but were impaired in the ability to distinguish two similar contexts. A significant reduction in the context-specific modulation of firing rate was observed in the CA3 pyramidal cells when the mutant mice were transferred from one context to another. These results provide evidence that NMDA receptors in the granule cells of the dentate gyrus play a crucial role in the process of pattern separation.

The medial temporal lobe, including the hippocampus, has been implicated in social memory. However, it remains unknown which parts of these brain regions and their circuits hold social memory. Here, we show that ventral hippocampal CA1 (vCA1) neurons of a mouse and their projections to nucleus accumbens (NAc) shell play a necessary and sufficient role in social memory. Both the proportion of activated vCA1 cells and the strength and stability of the responding cells are greater in response to a familiar mouse than to a previously unencountered mouse. Optogenetic reactivation of vCA1 neurons that respond to the familiar mouse enabled memory retrieval and the association of these neurons with unconditioned stimuli. Thus, vCA1 neurons and their NAc shell projections are a component of the storage site of social memory.