Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut, USA.
J Clin Invest. 2018 Jul 2;128(7):2757-2759. doi: 10.1172/JCI121653. Epub 2018 Jun 18.
The ability to recognize and avoid noxious stimuli is essential for survival. The factors that determine whether a given stimulus is considered positive or negative are complex and not fully understood. In this issue of the JCI, Klawonn and colleagues demonstrate that melanocortin 4 receptor (MC4R) signaling is critical for proper responses to negative stimuli. Mice lacking MC4R were shown to have a surprising preference for aversive stimuli compared with WT animals. Moreover, the authors provide evidence that avoidance behaviors are mediated by hypothalamic POMC neurons signaling to striatal dopamine D1 receptor-expressing medium spiny neurons. Together, these results provide important insight into the regulation of responses to aversive stimuli.
识别和避免有害刺激对于生存至关重要。决定给定刺激是正面还是负面的因素很复杂，目前尚未完全了解。在本期 JCI 中，Klawonn 及其同事证明了黑皮质素 4 受体 (MC4R) 信号对于对负面刺激做出适当反应至关重要。研究表明，缺乏 MC4R 的小鼠与 WT 动物相比，对厌恶刺激表现出惊人的偏好。此外，作者提供的证据表明，回避行为是由下丘脑 POMC 神经元向纹状体多巴胺 D1 受体表达的中间棘神经元发出信号来介导的。这些结果共同为调节对厌恶刺激的反应提供了重要的见解。
