Elucidating an Affective Pain Circuit that Creates a Threat Memory.
Elucidating an Affective Pain Circuit that Creates a Threat Memory.
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阐明产生威胁记忆的情感疼痛回路
DOI：
10.1016/j.cell.2015.05.057
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发表时间：
2015-07-16
期刊：
影响因子：
64.5
通讯作者：
Palmiter RD
中科院分区：
文献类型：
--
作者：
Han S;Soleiman MT;Soden ME;Zweifel LS;Palmiter RD
动物通过将中性刺激与痛苦的刺激联系在一起来学习避免有害的情况，从而产生稳定的威胁记忆。在哺乳动物中，这种形式的学习需要杏仁核。虽然疼痛是厌恶学习的主要驱动力，但将疼痛信号传递到杏仁核的机制尚未很好地解决。在这里，我们发现在臂旁核表达降钙素基因相关肽(CGRP)的神经元是将疼痛信号传递到杏仁中央核的关键，这一途径可能传递疼痛的情感动机方面。CGRP神经元的遗传沉默阻止了疼痛反应和记忆的形成，而它们的光遗传刺激产生了防御反应和威胁记忆。中央杏仁核中表达CGRP受体的痛觉感受器神经元对于建立威胁记忆也是至关重要的。识别传递情感疼痛信号的神经回路对于治疗患有精神疾病的疼痛状况可能是有意义的。
Animals learn to avoid harmful situations by associating a neutral stimulus with a painful one, resulting in a stable threat memory. In mammals, this form of learning requires the amygdala. Although pain is the main driver of aversive learning, the mechanism that transmits pain signals to the amygdala is not well resolved. Here we show that neurons expressing calcitonin gene-related peptide (CGRP) in the parabrachial nucleus are critical for relaying pain signals to the central nucleus of amygdala, and that this pathway may transduce the affective motivational aspects of pain. Genetic silencing of CGRP neurons blocks pain responses and memory formation, while their optogenetic stimulation produces defensive responses and a threat memory. The pain-recipient neurons in the central amygdala expressing CGRP receptors are also critical for establishing a threat memory. The identification of the neural circuit conveying affective pain signals may be pertinent for treating pain conditions with psychiatric comorbidities.