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解析大鼠杏仁中央核 CRF 神经元中 GABA 和神经肽在焦虑和恐惧学习中的作用。

Dissecting the Roles of GABA and Neuropeptides from Rat Central Amygdala CRF Neurons in Anxiety and Fear Learning.

机构信息

Department of Neuroscience, University of Texas at Austin, Austin, TX 78712, USA; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

Department of Neuroscience, University of Texas at Austin, Austin, TX 78712, USA; Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.

出版信息

Cell Rep. 2019 Oct 1;29(1):13-21.e4. doi: 10.1016/j.celrep.2019.08.083.

DOI:10.1016/j.celrep.2019.08.083
PMID:31577943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6879108/
Abstract

Central amygdala (CeA) neurons that produce corticotropin-releasing factor (CRF) regulate anxiety and fear learning. These CeA neurons release GABA and several neuropeptides predicted to play important yet opposing roles in these behaviors. We dissected the relative roles of GABA, CRF, dynorphin, and neurotensin in CeA neurons in anxiety and fear learning by disrupting their expression using RNAi in male rats. GABA, but not CRF, dynorphin, or neurotensin, regulates baseline anxiety-like behavior. In contrast, chemogenetic stimulation of CeA neurons evokes anxiety-like behavior dependent on CRF and dynorphin, but not neurotensin. Finally, knockdown of CRF and dynorphin impairs fear learning, whereas knockdown of neurotensin enhances it. Our results demonstrate distinct behavioral roles for GABA, CRF, dynorphin, and neurotensin in a subpopulation of CeA neurons. These results highlight the importance of considering the repertoire of signaling molecules released from a given neuronal population when studying the circuit basis of behavior.

摘要

杏仁中央核(CeA)中产生促肾上腺皮质释放因子(CRF)的神经元调节焦虑和恐惧学习。这些 CeA 神经元释放 GABA 和几种神经肽,据预测它们在这些行为中发挥着重要但相反的作用。我们通过在雄性大鼠中使用 RNAi 干扰其表达,剖析了 GABA、CRF、强啡肽和神经降压素在 CeA 神经元中在焦虑和恐惧学习中的相对作用。GABA 而非 CRF、强啡肽或神经降压素调节基线焦虑样行为。相比之下,CeA 神经元的化学遗传刺激会引发依赖于 CRF 和强啡肽但不依赖于神经降压素的焦虑样行为。最后,CRF 和强啡肽的敲低会损害恐惧学习,而神经降压素的敲低会增强恐惧学习。我们的研究结果表明 GABA、CRF、强啡肽和神经降压素在 CeA 神经元的一个亚群中具有不同的行为作用。这些结果突出了在研究行为的电路基础时考虑给定神经元群体释放的信号分子的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/b4fb909a1aec/nihms-1543429-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/a0409f1cf238/nihms-1543429-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/1ed9be804d13/nihms-1543429-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/e90e013e19e8/nihms-1543429-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/b4fb909a1aec/nihms-1543429-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/a0409f1cf238/nihms-1543429-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/1ed9be804d13/nihms-1543429-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/e90e013e19e8/nihms-1543429-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e82e/6879108/b4fb909a1aec/nihms-1543429-f0005.jpg

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