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bioRxiv · 10.1101/833723

Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a mouse model of schizophrenia

Donegan, M. L.·Stefanini, F.·Meira, T.·Gordon, J. A.·Fusi, S.·Siegelbaum, S. A.
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Abstract

The hippocampal CA2 region is essential for social memory and has been implicated in neuropsychiatric disorders. However, little is known about how CA2 neural activity encodes social interactions and how this coding is altered in disease. We recorded from CA2 pyramidal neurons as mice engaged in social interactions and found that while CA2 failed to stably represent spatial location, CA2 activity encoded contextual changes and novel social stimuli. In the Df(16)A+/- mouse model of the human 22q11.2 microdeletion, a major schizophrenia risk factor, CA2 activity showed a surprising increase in spatial coding while failing to encode social novelty, consistent with the social memory deficit in these mice. Previous work has shown that CA2 pyramidal neurons are hyperpolarized in Df(16)A+/- mice, likely as a result of upregulation of TREK-1 K+ current. We found that administration of a TREK-1 antagonist rescued the social memory deficits and restored normal CA2 coding properties in Df(16)A+/- mice, supporting a crucial role for CA2 in the encoding of novel social stimuli and social dysfunction.

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Donegan, M. L., Stefanini, F., Meira, T., Gordon, J. A., Fusi, S., Siegelbaum, S. A.. 2019-11-07. Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a mouse model of schizophrenia. https://doi.org/10.1101/833723

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