Adult hippocampal glucocorticoid receptor expression and dentate synaptic plasticity correlate with maternal care received by individuals early in life

Maternal care in mammals is the prevailing environmental influence during perinatal development. The adult rat offspring of mothers exhibiting increased levels of pup licking/grooming (LG; High LG mothers), compared to those reared by Low LG dams, show increased hippocampal glucocorticoid receptor expression, complex dendritic tree structure, and an enhanced capacity for synaptic potentiation. However, these data were derived from studies using the total amount of maternal care directed toward the entire litter, thus ignoring possible within-litter variation. We show that the amount of LG received by individual pups within a litter varies considerably. Therefore, we questioned if the amount of LG received by individual pups correlates with and thus putatively predicts later hippocampal structure and function. To this end, LG-scores were determined during the first postnatal week for all pups in 32 litters and correlated with neuroendocrine and hippocampal parameters in young-adulthood. Pup LG-score positively correlated with the glucocorticoid receptor mRNA expression in the adult hippocampus. Moreover, the ability to induce synaptic potentiation in the dentate gyrus in vitro was enhanced in animals with high LG-scores. Structural plasticity correlated less reliably with LG-scores early in life and differed between sexes. Male offspring with high LG-scores displayed fewer newborn neurons, higher brain derived neurotrophic factor expression and tended to have more complex granule cell dendritic trees. We conclude that even moderate variations in early life environment have a major impact on adult hippocampal function. This principle could provide a mechanistic basis for individual differences in susceptibility to psychopathology.