Early life experience can significantly determine later mental health status and cognitive function. Neonatal stress, in particular, has been linked to the etiology of mental health disorders as divergent as mood disorder, schizophrenia, and autism. Our study uses a Balb/CByJ mouse model to test the hypothesis, that neonatal stress will alter development and subsequent environmental modulation of neocortex. Using a split litter design, we generated stressed mice (STR) and within litter controls (LMC) along with age-matched, untreated animals (AMC), to serve as across litter controls. Short, daily exposure to a psychosocial/physical stressor, during the first week of life, resulted by adulthood in significant changes in neocortical thickness and architecture, which were further modulated by exposure to behavioral testing. Surprisingly, cortical size in LMC mice was also affected. These observations were compared to the effects of environmental enrichment in the same mouse strain. Our data indicate that LMC and STR males share with environmentally enriched males, an increase in thickness in infra-granular cortical layers, while STR also display a stress selective decrease in supragranular layers, in response to behavioral training as adults.
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