Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Neuron. 2019 Jul 17;103(2):309-322.e7. doi: 10.1016/j.neuron.2019.04.035. Epub 2019 May 28.
Body temperature control is essential for survival. In mammals, thermoregulation is mediated by the preoptic area of anterior hypothalamus (POA), with ∼30% of its neurons sensitive to brain temperature change. It is still unknown whether and how these temperature-sensitive neurons are involved in thermoregulation, because for eight decades they have only been identified via electrophysiological recording. By combining single-cell RNA-seq with whole-cell patch-clamp recordings, we identified Ptgds as a genetic marker for temperature-sensitive POA neurons. Then, we demonstrated these neurons' role in thermoregulation via chemogenetics. Given that Ptgds encodes the enzyme that synthesizes prostaglandin D2 (PGD), we further explored its role in thermoregulation. Our study revealed that rising temperature of POA alters the activity of Ptgds-expressing neurons so as to increase PGD production. PGD activates its receptor DP1 and excites downstream neurons in the ventral medial preoptic area (vMPO) that mediates body temperature decrease, a negative feedback loop for thermoregulation.
体温控制对生存至关重要。在哺乳动物中，体温调节是由下丘脑前视前区（POA）介导的，其中约 30%的神经元对脑温变化敏感。这些温度敏感神经元是否以及如何参与体温调节仍然未知，因为在过去的 80 年里，它们仅通过电生理记录来识别。通过结合单细胞 RNA-seq 和全细胞膜片钳记录，我们确定 Ptgds 是 POA 温度敏感神经元的遗传标志物。然后，我们通过化学遗传学证明了这些神经元在体温调节中的作用。鉴于 Ptgds 编码合成前列腺素 D2 (PGD) 的酶，我们进一步探讨了其在体温调节中的作用。我们的研究表明，POA 温度的升高改变了表达 Ptgds 的神经元的活性，从而增加了 PGD 的产生。PGD 激活其受体 DP1 并兴奋腹内侧视前区（vMPO）中的下游神经元，介导体温下降，这是体温调节的负反馈回路。
