Within- and between-litter maternal care alter behavior and gene regulation in female offspring

Rat dams show natural variations in maternal care, licking and grooming (LG), that are associated with distinct behavioral and neural phenotypes in offspring. However, there has been limited research on the effects of differences in LG received by female pups and of variations in maternal care within the litter. Here, we investigated LG received by measuring active maternal care after pup retrieval of female offspring. We then examined locomotor activity, open field exploration, and restraint stress reactivity in adult female offspring. We also investigated the expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) and DNA methylation of the GR17 promoter in the hippocampus. High compared with low LG siblings and female offspring from high compared with low LG dams showed increased locomotor activity. High compared with low LG siblings also showed reduced anxiety behavior regardless of the overall level of LG received in the litter. Unexpectedly, both the lowest licked offspring from low LG litters and the highest licked offspring from high LG litters showed suppressed corticosterone (CORT) responses to stress. However, high LG offspring within litters also showed increased expression of the GR gene, which was negatively correlated with the CORT response to restraint. DNA methylation at 2 CpG sites within GR17 promoter was significantly higher in high LG offspring. These differences in the response to maternal care both within- and between-litters were distinct in part from previous reports of between litter effects, potentially a result of the sex studied or the methods used to observe maternal care.