Coding of social novelty in the hippocampal CA2 region and its disruption and rescue in a 22q11.2 microdeletion mouse model

Donegan et al. show that hippocampal CA2 neurons contribute to social memory by encoding social novelty. Abnormal CA2 coding and social memory in a mouse model of the 22q11.2 microdeletion are rescued by blocking elevated CA2 TREK-1 K(+)current. The hippocampal CA2 region is essential for social memory. To determine whether CA2 activity encodes social interactions, we recorded extracellularly from CA2 pyramidal neurons (PNs) in male mice during social behavior. Although CA2 neuronal firing showed only weak spatial selectivity, it accurately encoded contextual changes and distinguished between a novel and a familiar mouse. In theDf(16)A(+/-)mouse model of the human 22q11.2 microdeletion, which confers a 30-fold increased risk of schizophrenia, CA2 social coding was impaired, consistent with the social memory deficit observed in these mice; in contrast, spatial coding accuracy was greatly enhanced. CA2 PNs were previously found to be hyperpolarized inDf(16)A(+/-)mice, likely due to upregulation of TREK-1 K(+)current. We found that TREK-1 blockade rescued social memory and CA2 social coding inDf(16)A(+/-)mice, supporting a crucial role for CA2 in the normal encoding of social stimuli and in social behavioral dysfunction in disease.