Developmental Changes in Functional Connectivity between the Prefrontal Cortex and Amygdala following Fear Extinction.

The amygdala and prefrontal cortex (PFC) undergo dramatic changes in structure, function, and regional connectivity in early life, ultimately stabilizing in early adulthood. Pathways between these two structures underlie many forms of emotional learning, including the extinction of conditioned fear. Here we sought to characterize changes in extinction-related medial PFC (mPFC)→ amygdala functional connectivity across development that might explain adolescent impairments in extinction. The retrograde tracer Fluorogold was infused into the amygdala of postnatal day (P)22-23 (juvenile), P31-32 (adolescent), or ≥P69 (adult) rats, which were then exposed to fear conditioning and extinction training. Brains were collected following extinction or context exposure and processed for expression of pMAPK (as a marker of learning-dependent plasticity) in prelimbic (PL) and infralimbic (IL) amygdala-projecting neurons. Consistent with previous findings, amygdala-projecting mPFC neurons were located primarily in layers (L)II/III and V of the mPFC. We noted that mPFC LII/III projected predominantly to the ipsilateral basolateral amygdala, whereas LV projected bilaterally and targeted multiple amygdalar nuclei. Extinction was not associated with changes in extinction-related plasticity in the PL-amygdala pathways in any age group. No changes were seen in LII/III of the IL, but extinction-related plasticity in LV amygdala-projecting IL neurons decreased linearly across development. These findings suggest that extinction-related functional connectivity between the IL and the amygdala undergoes fundamental changes across development that may contribute to alterations in fear suppression across development.