A novel spinal neuron connection for heat sensation

Heat perception enables acute avoidance responses to prevent tissue damage and maintain body thermal ho-meostasis. Unlike other modalities, how heat signals are processed in the spinal cord remains unclear. By sin-gle-cell gene profiling, we identified ErbB4, a transmembrane tyrosine kinase, as a novel marker of heat -sensi-tive 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 hy-persensitivity 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.

Automated summary

A study has identified ErBB4 as a marker for heat-sensitive spinal neurons in mice, which receive inputs from nociceptors and form excitatory synapses onto target neurons. Activation of these neurons enhances heat response, while inhibition reduces it. NRG1 regulates this process by promoting glutamatergic transmission through the dynamic activity of the tyrosine kinase. This research reveals the spinal neuron connection and regulatory mechanism of heat sensation involving the NRG1-ErBB4 signaling.