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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

利用光遗传学阐明恐惧学习过程中控制厌恶信息处理的神经回路

基本信息

批准号：
16J10802
负责人：
YEH LI FENG
金额：
$ 0.83万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for JSPS Fellows
财政年份：
2016
资助国家：
日本
起止时间：
2016-04-22 至 2018-03-31
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16J10802/
关键词：
fear learning periaqueductal grey amygdala thalamus fear memory

项目摘要

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.

该项目旨在了解触发恐惧学习的厌恶回路。我假设厌恶信号通过丘脑中线和板内核团传递。首先，我绘制了丘脑不同中线核团的输入输出通路。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)发送投射。背外侧PAG(DlPAG)神经元优先靶向丘脑前中线(AMT)。相反，腹大PAG(VlPAG)神经元强烈投射到丘脑后中线(PMT)。厌恶刺激引起丘脑中线LA/B投射神经元即刻基因表达(c-fos)。这些结果表明，中线丘脑向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，并在恐惧条件反射过程中光遗传干扰厌恶信号。光遗传抑制dlPAG-AMT神经元减弱了恐惧学习；然而，抑制其他PAG-丘脑回路对学习没有影响。结果表明，PAG-丘脑环路在解剖和功能上存在分离。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是如何到达LA/B区来诱导恐惧学习的，从而促进了对情绪学习和适应行为的回路机制的理解。