Tan Chan Lek, Cooke Elizabeth K, Leib David E, Lin Yen-Chu, Daly Gwendolyn E, Zimmerman Christopher A, Knight Zachary A
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94158, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Cell. 2016 Sep 22;167(1):47-59.e15. doi: 10.1016/j.cell.2016.08.028. Epub 2016 Sep 8.
Thermoregulation is one of the most vital functions of the brain, but how temperature information is converted into homeostatic responses remains unknown. Here, we use an unbiased approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that orchestrate the homeostatic response to heat. We show that these WSNs are molecularly defined by co-expression of the neuropeptides BDNF and PACAP. Optical recordings in awake, behaving mice reveal that these neurons are selectively activated by environmental warmth. Optogenetic excitation of WSNs triggers rapid hypothermia, mediated by reciprocal changes in heat production and loss, as well as dramatic cold-seeking behavior. Projection-specific manipulations demonstrate that these distinct effectors are controlled by anatomically segregated pathways. These findings reveal a molecularly defined cell type that coordinates the diverse behavioral and autonomic responses to heat. Identification of these warm-sensitive cells provides genetic access to the core neural circuit regulating the body temperature of mammals. PAPERCLIP.
体温调节是大脑最重要的功能之一，但温度信息如何转化为稳态反应仍不清楚。在这里，我们采用一种无偏向性的依赖活动的RNA测序方法，来识别视前下丘脑内协调对热的稳态反应的温敏神经元（WSNs）。我们表明，这些WSNs在分子水平上由神经肽BDNF和PACAP的共表达所定义。对清醒行为小鼠的光学记录显示，这些神经元被环境温暖选择性激活。对WSNs的光遗传学激发引发快速体温过低，这由产热和散热的相互变化以及剧烈的畏寒行为介导。特定投射操作表明，这些不同的效应器由解剖学上分离的通路控制。这些发现揭示了一种在分子水平上定义的细胞类型，它协调对热的多种行为和自主反应。识别这些温敏细胞为调控哺乳动物体温的核心神经回路提供了遗传通路。回形针。
