Prefrontal cortical inputs to the basal amygdala undergo pruning during late adolescence in the rat

Abstract

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.

Postnatal development of the amygdala: A stereological study in rats

“…Other studies have suggested a decrease in neuropil volume in the medial amygdala during puberty in the rat (Zehr et al, 2006). Similarly, a tracttracing study, using both retrograde and anterograde tracers, has shown that mPFC projections to the basal and accessory basal nuclei decrease between P25 and P90 in rats (Cressman et al, 2010).…”

Extinction and reinstatement to cocaine-associated cues in male and female juvenile rats and the role of D1 dopamine receptor

“…In addition, BLA activity also facilitates extinction (Schroeder and Packard, 2003, 2004). As the PFC innervates the BLA by 28 and 45 days (Cressman et al, 2010), elevated D1 in the plPFC could facilitate extinction by modulating the BLA. D1 enhancement of the function of these connections could increase extinction in the juveniles.…”

Sensitive Periods in Affective Development: Nonlinear Maturation of Fear Learning

“…However, the pronounced structural remodeling of subcortical-prefrontal connections (eg myelination, synaptic pruning) that occurs during adolescence is likely to contribute to these qualitative shifts in fear expression (Somerville and Casey, 2010;Spear, 2000). For example, there is substantial pruning of neurons projecting from the IL to the basal amygdala from adolescence to adulthood (Cressman et al, 2010). Changes in connectivity between both the amygdala and the hippocampus, and the IL and PL during adolescence may initiate the shift from the restricted subcortical circuitry governing fear learning in juvenile stages, toward the more flexible and expansive circuit for fear regulation that is evident in adulthood.…”