Interhemispheric CA1 projections to the subiculum support spatial cognition and are affected in a mouse model of the 22q11.2 deletion syndrome

Mapping hippocampal connectivity is essential to understand the neural mechanisms of learning and memory, yet interhemispheric connections between hippocampal formations remain poorly defined. In rodents, two main commissural pathways are known: dentate gyrus hilar mossy cells project to the inner molecular layer of the contralateral dentate gyrus, and CA2/CA3 pyramidal neurons send collaterals to contralateral CA3, CA2, and CA1 regions. By contrast, commissural outputs from CA1 remain largely unexplored. Here, we show that dorsal CA1 (dCA1) pyramidal neurons located in the right hemisphere project to contralateral dorsal subiculum (dSUB) in addition to contralateral dCA1. We then assess the function of the projection from the right dCA1 to the left dSUB and find that this interhemispheric pathway supports spatial memory and spatial working memory, two cognitive functions altered in the Df16(A)^+/- mouse model of 22q11.2 deletion syndrome (22q11.2DS) associated with schizophrenia. Notably, the right-to-left dCA1 interhemispheric projections are disrupted in Df16(A)^+/- mice, suggesting that dysregulation of this circuit may contribute to 22q11.2DS-related cognitive deficits.