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.

杏仁核和前额叶皮层 (PFC) 在生命早期的结构、功能和区域连接方面经历了巨大的变化，最终在成年早期趋于稳定。这两种结构之间的通路是许多形式的情绪学习的基础，包括条件性恐惧的消除。在这里，我们试图描述与灭绝相关的内侧 PFC（mPFC）→ 杏仁核功能连接在整个发育过程中的变化，这可能解释青少年在灭绝中的损伤。将逆行示踪剂 Fluorogold 注入出生后第 22-23 天（幼年）、P31-32（青少年）或≥P69（成年）大鼠的杏仁核，然后对其进行恐惧调节和消退训练。在灭绝或环境暴露后收集大脑，并进行处理以在边缘前 (PL) 和边缘下 (IL) 杏仁核投射神经元中表达 pMAPK（作为学习依赖性可塑性的标记）。与之前的发现一致，杏仁核投射的 mPFC 神经元主要位于 mPFC 的 (L)II/III 和 V 层。我们注意到 mPFC LII/III 主要投射到同侧基底外侧杏仁核，而 LV 投射到双侧并针对多个杏仁核。在任何年龄组中，灭绝与 PL-杏仁核通路中与灭绝相关的可塑性变化无关。IL 的 LII/III 没有变化，但左心室杏仁核投射的 IL 神经元的消退相关可塑性在发育过程中线性下降。这些发现表明，IL 和杏仁核之间与灭绝相关的功能连接在发育过程中经历了根本性的变化，这可能有助于在发育过程中恐惧抑制的改变。