Cellular and synaptic mechanisms underlying how chronic pain induces maladaptive alterations to local circuits in the medial prefrontal cortex (mPFC), while emerging, remain unresolved. Consistent evidence shows that chronic pain attenuates activity in the prelimbic (PL) cortex, a mPFC subregion. This reduced activity is thought to be driven by increased inhibitory tone within PL circuits. Enhanced input from the basolateral amygdala (BLA) to inhibitory neurons in PL cortex is one well-received mechanism for this circuit change. In mice, we used retrograde labeling, brain slice recordings, and optogenetics to selectively stimulate and record ascending BLA inputs onto PL neurons that send projections to the periaqueductal gray (PAG), which is a midbrain structure that plays a significant role in endogenous analgesia. Activating BLA projections evoked both excitatory and inhibitory currents in cortico-PAG (CP) neurons, as we have shown previously. We measured changes to the ratio of BLA-evoked excitatory to inhibitory currents in the spared nerve injury (SNI) model of neuropathic pain. Our analysis reveals a reduced excitation-inhibition (E/I) ratio of BLA inputs to PL-CP neurons 7 days after SNI. The E/I ratio of BLA inputs to CP neurons in neighboring infralimbic (IL) cortex was unchanged in SNI animals. Collectively, this study reveals that the overall E/I balance of BLA inputs to PL neurons projecting to the PAG is reduced in a robust neuropathic pain model. Overall, our findings provide new mechanistic insight into how nerve injury produces dysfunction in PL circuits connected to structures involved in pain modulation.

中文翻译：

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周围神经损伤降低了基底外侧扁桃体输入到投射至导水管周围灰色的前缘锥体神经元的兴奋抑制平衡。

慢性疼痛如何诱发前额内侧皮层（mPFC）局部回路适应不良的改变的细胞和突触机制，尽管仍未解决。一致的证据表明，慢性疼痛会削弱前边缘（PL）皮质mPFC子区域的活动。人们认为这种降低的活性是由PL回路中抑制音的增加所驱动的。从基底外侧杏仁核（BLA）到PL皮质中抑制性神经元的增强输入是这种电路改变的一种广为接受的机制。在小鼠中，我们使用了逆行标记，脑切片记录和光遗传学技术，选择性地刺激和记录了PL神经元上的BLA输入，这些输入将投影投射到导水管周围的灰色（PAG），这是中脑结构，在内源性镇痛中起重要作用。如我们先前所示，激活的BLA投射引起皮质PAG（CP）神经元的兴奋性电流和抑制性电流。我们在神经性疼痛的备用神经损伤（SNI）模型中测量了BLA诱发的兴奋性与抑制性电流之比的变化。我们的分析显示SNI后7天，BLA输入与PL-CP神经元的兴奋抑制（E / I）比率降低。在SNI动物中，邻近的下肢（IL）皮质中BLA输入与CP神经元的E / I比没有变化。总的来说，这项研究表明，在健壮的神经性疼痛模型中，BLA输入到投射到PAG的PL神经元的总E / I平衡降低了。总体而言，我们的发现为神经损伤如何导致与疼痛调节相关结构相连的PL电路功能障碍提供了新的机制。