Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice
Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice
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DOI：
10.1186/s13041-019-0529-1
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发表时间：
2019-12-04
期刊：
影响因子：
3.6
通讯作者：
Zamponi, Gerald W.
中科院分区：
文献类型：
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作者：
Gadotti, Vinicius M.;Zhang, Zizhen;Zamponi, Gerald W.
周围神经损伤会导致脑回路重塑，从而导致疼痛慢性化。我们最近报道，坐骨神经未受损伤的雄性小鼠的内侧前额皮质 (mPFC) 功能发生变化，最终导致第 5 层锥体细胞的输出减少。最近，我们发现这是通过从基底外侧杏仁核 (BLA) 到 mPFC 中 GABA 能中间神经元的突触输入的改变来介导的。这些输入的光遗传学抑制逆转了雄性小鼠的机械异常性疼痛和热痛觉过敏。众所周知，疼痛信号的处理可以表现出明显的性别差异。因此，我们测试了 BLA 对 mPFC 信号传导的失调在雌性小鼠中是否也发生了同样的改变。将 AAV-Arch3.0 构建体注射到 BLA 中，然后将光纤插管植入假手术和 SNI 操作的雌性小鼠的 mPFC 中，并测量响应黄光介导的这种抑制性视蛋白激活的疼痛行为反应。我们的数据显示，Arch3.0 激活分别导致机械和热刺激的缩爪阈值和延迟显着增加。然而，我们没有观察到神经损伤引起雌性小鼠 mPFC 第 5 层锥体细胞输出的变化。因此，观察到的光诱导镇痛作用可能是由于 mPFC 下游神经元回路失调的补偿所致。
Peripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.