Early life stress is known to induce long-term alterations in
emotional and anxiety-related behaviors. Rodent models of neonatal maternal separation (MS) stress have been used to explore the effects of early stress on changes in affective and cognitive behaviors. MS are associated with structural changes in brain regions linked to cognition and mood regulation, including the amygdala and the hippocampus. Here, we studied the effects of MS on neurogenesis in the hippocampus and amygdala and correlated the changes in the neurogenesis with behavioral alterations. The MS was performed daily for 3 hr from P1 to P14 and litter control pups were left undisturbed and mice were subjected to behavioral test starting at 10 weeks of age. We used a battery of stress and anxiety-related behavioral tests (i.e., the open field, startle and prepulse inhibition (PPI), and fear conditioning) in C57Bl/6 mice. The open field test, which measures the basal anxiety level, showed that MS mice spent less time in the center area in the open field test, although total moving distance did not differ. The contextual and cued fear conditioning test, which provides a measure of memory by assessing a memory for the association between an aversive stimulus and an auditory cue, suggests that the expression of fearfulness was altered in the MS mice.
After the completion of behavioral batteries, we examined the neurogenesis in the dentate gyrus of hippocampus and amygdala and found that MS increased it. These results suggest that neonatal MS treatment enhances the neurogenesis in the limbic system and alters the anxiety- and fear-related behavior.