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

In humans, 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 rodent models that expose litters to very different postnatal manipulations, but the effect of these paradigms on offspring through differences in maternal care and neuronal activation remains incompletely explored. To address this gap, we directly compared behavior of dams in MSEW and LBN conditions to control conditions. We found that LBN dams showed reduced duration of bouts on the nest, as well as increased exits from the nest and attempts at nest maintenance, whereas MSEW dams demonstrate control-like caregiving aside from the daily separations from the litter. At P7, MSEW and LBN pups showed distinct neuronal activation patterns in hippocampal subregions associated with social recognition memory. Next, we assessed social recognition memory at different developmental timepoints and found impairments after both ELA paradigms in both sexes at P21. After puberty, at P45, ELA females had improved social recognition memory while males remained impaired. Hippocampal plasticity measures known to participate in social recognition function in adults revealed age-, and sex-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 CA2 region of LBN offspring. These findings highlight differences between two ELA paradigms in maternal care, as well as neuronal activation, hippocampal plasticity measures, and social recognition memory in offspring.