恐怖学習中の嫌悪情報処理を司る神経回路の光遺伝学を用いた解明

该项目旨在了解引发恐惧学习的厌恶回路。我假设厌恶信号通过中线和丘脑板内核传递。首先，我绘制了不同中线丘脑核团的输入输出通路。几个中线丘脑区域接收PAG输入并将投射发送到外侧和基底杏仁核（LA/B）。背外侧PAG（dlPAG）神经元优先靶向前中线丘脑（aMT）。相反，腹侧PAG（vlPAG）神经元强烈投射到后中线丘脑（pMT）。厌恶性刺激（足电击）引起丘脑中线LA/B投射神经元的即刻基因表达（c-fos）。这些结果提示丘脑中线向LA/B传递厌恶信号。然后，我通过在PAG中表达抑制性视蛋白ArchT来靶向PAG-中线丘脑投射，并在恐惧条件反射期间光遗传学地破坏厌恶信号。dlPAG-aMT神经元的光遗传抑制减弱了恐惧学习;然而，其他PAG-丘脑回路的抑制对学习没有影响。结果表明，解剖和功能隔离PAG丘脑电路。也就是说，dlPAG中的aMT投射神经元对于在恐惧学习期间传递厌恶信号至关重要，而PAG和丘脑中的其他核团并不直接参与这一过程。总之，这些发现通过展示厌恶信息如何到达LA/B以诱导恐惧学习，推进了对情绪学习和适应行为的回路机制的理解。

The project aims at understanding the aversive circuits which trigger fear learning. I hypothesized that aversive signals are transmitted through the midline and intralaminar thalamic nuclei. First, I mapped the input-output pathways of various midline thalamic nuclei. Several midline thalamic regions receive PAG inputs and send projection to the lateral and basal amygdala (LA/B). Dorsolateral PAG (dlPAG) neurons preferentially target anterior midline thalamus (aMT). In contrast, ventrolareral PAG (vlPAG) neurons project strongly to the posterior midline thalamus (pMT). Aversive stimuli, namely footshocks, evoke the immediate gene expression (c-fos) in LA/B projection neurons of the midline thalamus. These results suggest that the midline thalamus transmits aversive signal to LA/B. I then targeted the PAG-midline thalamus projections by expressing inhibitory opsin ArchT in PAG, and optogenetically disrupted aversive signaling during fear conditioning. Optogenetic inhibition of dlPAG-aMT neurons attenuated fear learning; however, inhibition of other PAG-thalamus circuits had no effect on learning. The results demonstrate an anatomical and functional segregation in PAG-thalamus circuits. That is, the aMT-projecting neurons in dlPAG are critical for conveying aversive signals during fear learning, while other nuclei in PAG and thalamus do not contribute directly to this process. In sum, the findings advance the understanding of circuit mechanisms of emotional learning and adaptive behaviors by showing how aversive information reaches the LA/B to induce fear learning.