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Different early-life adversity paradigms have disparate effects on maternal care, neuronal activation, and social behavior in developing mice

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Apr 15, 2026 version files 18.53 GB

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Abstract

Early-life adversity (ELA) predisposes individuals to neuropsychiatric conditions, with different types of adverse experiences linked more strongly to certain maladaptive outcomes. Maternal separation with early weaning (MSEW) and limited bedding and nesting (LBN) are two widely used mouse models of ELA, however the effect of these paradigms on offspring through differences in rearing experiences including maternal care and neuronal activation remains incompletely explored. To address this, we investigated the differential effects of control, MSEW, and LBN rearing and found that LBN dams showed reduced duration of bouts on the nest, increased exits from the nest, and more attempts at nest maintenance, whereas MSEW dams showed control-like caregiving aside from the daily separations from the litter. On postnatal day 7, MSEW and LBN pups showed distinct neuronal activation patterns in hippocampal subregions associated with stress and social recognition. Further, assessment of social recognition in ELA offspring at different timepoints over development showed impairments after both ELA paradigms in both sexes at P21. After puberty, at P45, ELA females had improved social recognition while males remained impaired. Hippocampal plasticity measures in the dorsal hippocampus known to participate in social recognition function in adults showed age-specific alterations in neural stem cell density in the dentate gyrus of MSEW offspring, as well as alterations in parvalbumin-positive interneurons and perineuronal nets in the dorsal CA2 region of LBN offspring. Together these findings highlight differences between two ELA paradigms in maternal care, neuronal activation, hippocampal plasticity measures, and social recognition in offspring.