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

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.