Thermosensors expressed in peripheral somatosensory neurons sense a wide range of environmental temperatures. While thermosensors detecting cool, warm and hot temperatures have all been extensively characterized, little is known about those sensing cold temperatures. Though several candidate cold sensors have been proposed, none has been demonstrated to mediate cold sensing in somatosensory neurons in vivo, leaving a knowledge gap in thermosensation. Here we characterized mice lacking the kainate-type glutamate receptor GluK2, a mammalian homolog of the Caenorhabditis elegans cold sensor GLR-3. While GluK2 knockout mice respond normally to heat and mechanical stimuli, they exhibit a specific deficit in sensing cold but not cool temperatures. Further analysis supports a key role for GluK2 in sensing cold temperatures in somatosensory DRG neurons in the periphery. Our results reveal that GluK2—a glutamate-sensing chemoreceptor mediating synaptic transmission in the central nervous system—is co-opted as a cold-sensing thermoreceptor in the periphery.

外周体感神经元中表达的热传感器可感知各种环境温度。虽然检测冷、暖和热温度的热传感器都已被广泛表征，但人们对那些检测冷温度的热传感器知之甚少。尽管已经提出了几种候选冷传感器，但没有一种传感器被证明可以在体内介导体感神经元的冷感，从而在热感觉方面留下了知识空白。在这里，我们表征了缺乏红藻氨酸型谷氨酸受体 GluK2 的小鼠，GluK2 是秀丽隐杆线虫冷传感器 GLR-3的哺乳动物同源物。虽然 GluK2 基因敲除小鼠对热和机械刺激有正常反应，但它们在感知寒冷而非低温方面表现出特定的缺陷。进一步的分析支持 GluK2 在感知周围 DRG 体感神经元低温方面的关键作用。我们的结果表明，GluK2——一种介导中枢神经系统突触传递的谷氨酸感应化学感受器——被选为外周的冷觉温度感受器。