Xiao, R. & Xu, X. Z. S. Temperature sensation: from molecular thermosensors to neural circuits and coding principles. Annu. Rev. Physiol. 83, 205–230 (2021).

Article  CAS  PubMed  Google Scholar 

Palkar, R., Lippoldt, E. K. & McKemy, D. D. The molecular and cellular basis of thermosensation in mammals. Curr. Opin. Neurobiol. 34, 14–19 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vandewauw, I. et al. A TRP channel trio mediates acute noxious heat sensing. Nature 555, 662–666 (2018).

Article  ADS  CAS  PubMed  Google Scholar 

Tan, C. H. & McNaughton, P. A. The TRPM2 ion channel is required for sensitivity to warmth. Nature 536, 460–463 (2016).

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Song, K. et al. The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia. Science 353, 1393–1398 (2016).

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Bautista, D. M. et al. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature 448, 204–208 (2007).

Article  ADS  CAS  PubMed  Google Scholar 

Dhaka, A. et al. TRPM8 is required for cold sensation in mice. Neuron 54, 371–378 (2007).

Article  CAS  PubMed  Google Scholar 

Buijs, T. J. & McNaughton, P. A. The role of cold-sensitive ion channels in peripheral thermosensation. Front. Cell. Neurosci. 14, 262 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Traynelis, S. F. et al. Glutamate receptor ion channels: structure, regulation, and function. Pharm. Rev. 62, 405–496 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gong, J. et al. A cold-sensing receptor encoded by a glutamate receptor gene. Cell 178, 1375–1386 e1311 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fujita, F., Uchida, K., Takaishi, M., Sokabe, T. & Tominaga, M. Ambient temperature affects the temperature threshold for TRPM8 activation through interaction of phosphatidylinositol 4,5-bisphosphate. J. Neurosci. 33, 6154–6159 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

McKemy, D. D., Neuhausser, W. M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58 (2002).

Article  ADS  CAS  PubMed  Google Scholar 

Peier, A. M. et al. A TRP channel that senses cold stimuli and menthol. Cell 108, 705–715 (2002).

Article  CAS  PubMed  Google Scholar 

Bandell, M., Macpherson, L. J. & Patapoutian, A. From chills to chilis: mechanisms for thermosensation and chemesthesis via thermoTRPs. Curr. Opin. Neurobiol. 17, 490–497 (2007).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Usoskin, D. et al. Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing. Nat. Neurosci. 18, 145–153 (2015).

Article  CAS  PubMed  Google Scholar 

Sharma, N. et al. The emergence of transcriptional identity in somatosensory neurons. Nature 577, 392–398 (2020).

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Duan, B. et al. Identification of spinal circuits transmitting and gating mechanical pain. Cell 159, 1417–1432 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ma, Q. A functional subdivision within the somatosensory system and its implications for pain research. Neuron 110, 749–769 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Knowlton, W. M. et al. A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia. J. Neurosci. 33, 2837–2848 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mulle, C. et al. Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 392, 601–605 (1998).

Article  ADS  CAS  PubMed  Google Scholar 

Zhou, X. et al. Deletion of PIK3C3/Vps34 in sensory neurons causes rapid neurodegeneration by disrupting the endosomal but not the autophagic pathway. Proc. Natl Acad. Sci. USA 107, 9424–9429 (2010).

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Han, L. et al. Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness. Nat. Neurosci. 21, 324–328 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarria, I., Ling, J., Xu, G. Y. & Gu, J. G. Sensory discrimination between innocuous and noxious cold by TRPM8-expressing DRG neurons of rats. Mol. Pain 8, 79 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim, Y. S. et al. Coupled activation of primary sensory neurons contributes to chronic pain. Neuron 91, 1085–1096 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Emery, E. C. et al. In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP. Sci. Adv. 2, e1600990 (2016).

Article  ADS  PubMed  PubMed Central  Google Scholar 

Wang, F. et al. Sensory afferents use different coding strategies for heat and cold. Cell Rep. 23, 2001–2013 (2018).

Article  CAS  PubMed  Google Scholar 

Story, G. M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829 (2003).

Article  CAS  PubMed  Google Scholar 

Buijs, T. J., Vilar, B., Tan, C. H. & McNaughton, P. A. STIM1 and ORAI1 form a novel cold transduction mechanism in sensory and sympathetic neurons. EMBO J. 42, e111348 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Zimmermann, K. et al. Transient receptor potential cation channel, subfamily C, member 5 (TRPC5) is a cold-transducer in the peripheral nervous system. Proc. Natl Acad. Sci. USA 108, 18114–18119 (2011).

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

MacDonald, D. I., Wood, J. N. & Emery, E. C. Molecular mechanisms of cold pain. Neurobiol. Pain 7, 100044 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Foulkes, T. & Wood, J. N. Mechanisms of cold pain. Channels (Austin) 1, 154–160 (2007).

Article  PubMed  Google Scholar 

Rodriguez-Moreno, A. & Lerma, J. Kainate receptor modulation of GABA release involves a metabotropic function. Neuron 20, 1211–1218 (1998).

Article  CAS  PubMed  Google Scholar 

Valbuena, S. & Lerma, J. Non-canonical signaling, the hidden life of ligand-gated ion channels. Neuron 92, 316–329 (2016).

Article  CAS  PubMed  Google Scholar 

Lerma, J. Roles and rules of kainate receptors in synaptic transmission. Nat. Rev. Neurosci. 4, 481–495 (2003).

Article  CAS  PubMed  Google Scholar 

Venkatachalam, K. & Montell, C. TRP channels. Annu. Rev. Biochem. 76, 387–417 (2007).

Article  CAS