Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6-120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo-cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood.

Growing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long-lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABAA receptor antagonist picrotoxin into the amygdala. The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2. The Nd of calbindin D28k (CB)-IR somata was decreased in CA3-2. The densities of axon terminals arising from PVB-IR and cholecystokinin (CCK)-IR basket neurons were also altered, with those of CCK-IR terminals increased across all sectors, while PVB-IR terminals were decreased only in the CA region. Increases in CCK-IR terminals were paralleled by increases of terminals with IR for the 65-kD isoform of glutamate decarboxylase (GAD65). Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far-reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus.

Previous work in animal models has shown that projections from the basolateral amygdala (BLA) progressively infiltrate the medial prefrontal cortex (mPFC) from birth to adulthood, with the most dramatic sprouting occurring during the postweanling period. GABAergic (gamma-aminobutyric acidergic) interneurons in the human homolog of the rat mPFC have been implicated in the pathophysiology of schizophrenia, an illness with an onset that is delayed until late adolescence. Here we investigated the interaction of BLA fibers with mPFC GABAergic interneurons from postnatal day 6 (P6) to P120 using anterograde tracing and immunocytochemistry. We found a 3-fold increase in axosomatic and an 8-fold increase in axo-dendritic contacts in both layers II and V of the mPFC. Ultrastructural analysis using a colloidal gold immunolocalization demonstrated that the greatest proportion of BLA appositions were with GABA-negative spines (30.8%) and GABA-positive dendritic shafts (35.5%). Although GABA-negative interactions demonstrated well-defined axo-spinous synapses, membrane specializations could not be identified with confidence in GABA-positive elements. Our findings suggest that GABAergic interneurons are major targets for BLA fibers projecting to the mPFC. The establishment of this circuitry, largely during adolescence, may contribute to the integration of emotional responses with attentional and other cognitive processes mediated within this region during corticolimbic development.