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。我假设厌恶信号是通过中线和层内丘脑核传递的。首先，我绘制了各种丘脑中线核的输入-输出通路。几个丘脑中线区域接受PAG输入并向外侧和基底杏仁核（LA/B）发送投影。背外侧PAG （dlPAG）神经元优先靶向丘脑前中线（aMT）。相反，腹侧PAG （vlPAG）神经元强烈地投射到丘脑后中线（pMT）。厌恶刺激，即脚震，唤起丘脑中线LA/B投射神经元的即时基因表达（c-fos）。这些结果表明丘脑中线向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-中线丘脑投影，并在恐惧条件反射过程中光遗传破坏厌恶信号。光遗传抑制dlPAG-aMT神经元对恐惧学习的减弱作用然而，抑制其他pag -丘脑回路对学习没有影响。结果表明，pag -丘脑回路存在解剖和功能上的分离。也就是说，在恐惧学习过程中，dlPAG中的amt投射神经元对传递厌恶信号至关重要，而PAG和丘脑中的其他核并不直接参与这一过程。总之，研究结果通过揭示厌恶信息如何到达LA/B诱发恐惧学习，促进了对情绪学习和适应行为回路机制的理解。

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.