1. A novel spinal neuron connection for heat sensation.
- Author
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Wang, Hongsheng, Chen, Wenbing, Dong, Zhaoqi, Xing, Guanglin, Cui, Wanpeng, Yao, Lingling, Zou, Wen-Jun, Robinson, Heath L., Bian, Yaoyao, Liu, Zhipeng, Zhao, Kai, Luo, Bin, Gao, Nannan, Zhang, Hongsheng, Ren, Xiao, Yu, Zheng, Meixiong, James, Xiong, Wen-Cheng, and Mei, Lin
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SENSES , *NEURONS , *KINASES , *PROTEIN-tyrosine kinases , *SPINAL cord , *NEUREGULINS - Abstract
Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal homeostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By single-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat-sensitive spinal neurons in mice. Ablating spinal ErbB4+ neurons attenuates heat sensation. These neurons receive monosynaptic inputs from TRPV1+ nociceptors and form excitatory synapses onto target neurons. Activation of ErbB4+ neurons enhances the heat response, while inhibition reduces the heat response. We showed that heat sensation is regulated by NRG1, an activator of ErbB4, and it involves dynamic activity of the tyrosine kinase that promotes glutamatergic transmission. Evidence indicates that the NRG1-ErbB4 signaling is also engaged in hypersensitivity of pathological pain. Together, these results identify a spinal neuron connection consisting of ErbB4+ neurons for heat sensation and reveal a regulatory mechanism by the NRG1-ErbB4 signaling. [Display omitted] • Spinal ErbB4+ neurons are activated by heat and synapsed by TRPV1+ nociceptors • Heat sensation is reduced by ErbB4+ neuron ablation or inhibition • Augmented effect on heat sensation by inhibiting ErbB4+, SST+, and CCK+ neurons together • NRG1-ErbB4 signaling promotes heat sensation and hypersensitivity How heat signals are processed in the spinal cord remains unclear. Wang et al. found that ErbB4+ excitatory interneurons are activated by noxious heat, and they participate in heat sensation in mice. In addition, the neuregulin-ErbB4 signaling regulates heat sensation and contributes to heat hypersensitivity under pathological conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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