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.

热感知能够实现敏锐的回避反应，以防止组织损伤并维持身体热稳态。与其他方式不同，热信号在脊髓中的处理方式仍不清楚。通过单细胞基因分析，我们确定了 ErbB4（一种跨膜酪氨酸激酶）作为小鼠热敏感脊髓神经元的新标记物。消融脊髓 ErbB4+ 神经元会减弱热感。这些神经元接收来自 TRPV1+ 伤害感受器的单突触输入，并在目标神经元上形成兴奋性突触。ErbB4+ 神经元的激活增强热反应，而抑制则降低热反应。我们发现热感觉受到 ErbB4 激活剂 NRG1 的调节，并且涉及促进谷氨酸能传递的酪氨酸激酶的动态活性。有证据表明 NRG1-ErbB4 信号传导也参与病理性疼痛的超敏反应。总之，这些结果确定了由 ErbB4+ 神经元组成的用于热感觉的脊髓神经元连接，并揭示了 NRG1-ErbB4 信号传导的调节机制。