Transformations in affective and social behaviors, many of which involve amygdalar circuits, are hallmarks of adolescence in many mammalian species. In this study, using the rat as a model, we provide the first evidence that afferents of the basal amygdala (BA) undergo significant structural remodeling during adolescence. We used quantitative tract-tracing and gene expression profiling methods to characterize changes in the medial prefrontal cortical (mPFC) inputs to the BA across ages analogous to the late juvenile period [postnatal day (P) 25], late adolescence (P45), and adulthood (P90) in the rat. As assessed after deposition of Fluorogold into the BA, the number of BA-projecting neurons in the mPFC remained stable between P25 and P45 but decreased by about 50% between P45 and P90. Anterograde tract tracing with biotin dextran amine deposits centered in the ventral prelimbic cortex revealed that, during this period, the density of mPFC-derived axon terminals in the BA also decrease significantly, an effect particularly evident in the dorsal basolateral nucleus. Within the BA, there were also highly significant changes in gene expression indicative of neurite or synaptic plasticity, most notably in the Ras/GTPase superfamily, and in pathways that regulate cytoskeletal dynamics and steroid synthesis/lipid metabolism. These data provide convergent evidence that mPFC inputs to the BA are pruned during late adolescence or early adulthood. Moreover, the structural remodeling within these afferents may be accompanied by significant changes in neurite plasticity within the BA.

Severe psychological stress in the first trimester of pregnancy increases the risk of schizophrenia in the offspring. To begin to investigate the role of glucocorticoid receptors in this association, we determined the effects of the glucocorticoid dexamethasone (2 mg/kg), administered to pregnant rats on gestation days 6-8, on maternal behaviors and schizophrenia-relevant behaviors in the offspring. Dams receiving dexamethasone exhibited increased milk ejection bouts during nursing. Offspring of dexamethasone-treated dams (DEX) showed decreased juvenile social play and a blunted acoustic startle reflex in adolescence and adulthood, effects that were predicted by frequency of milk ejections in the dams. DEX offspring also showed increased prepulse inhibition of startle and reduced amphetamine-induced motor activity, effects not correlated with maternal behavior. It is postulated that over-stimulation of receptors targeted by glucocorticoids in the placenta or other maternal tissues during early gestation can lead to psychomotor and social behavioral deficits in the offspring. Moreover, some of these deficits may be mediated by alterations in postnatal maternal behavior and physiology produced by early gestational exposure to excess glucocorticoids.

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