Maternal deprivation impairs social recognition by diminishing the number of adult-born granule cells in the dentate gyrus

Abstract

Childhood neglect increases the likelihood of developing neuropsychiatric disease in adulthood. Maternal separation and early weaning (MSEW), a rodent model of maternal deprivation, was used to investigate effects on social recognition, a commonly impaired function in neuropsychiatric disorders in humans. We found that in adulthood, MSEW male mice showed social recognition impairments, and that MSEW female mice showed greater preference fo social novelty. MSEW male, but not female, mice had diminished numbers of adult-born granule cells (abGCs) in the dentate gyrus, as well as a lower density of abGC axons in the CA2 region compared to controls. MSEW males also showed a reduced rate of sharp wave ripples (SWRs) in the CA2 region in response to novel mouse exposure, as well as a reduction in differential SWR rates in response to novel and familiar mouse exposure. Living in an enriched environment restored the number of abGCs in the dentate gyrus of MSEW males to control levels and improved social recognition. Furthermore, chemogenetic activation of 4-6 week old, but not older, abGCs in a double transgenic model improved social recognition and partially restored CA2 SWR patterns in MSEW mice. These findings suggest that MSEW impairs social recognition through diminished adult neurogenesis, which can be restored in adulthood by living in a proneurogenic environment or by increasing the activity of existing abGCs.