Warm-sensitive neurons that control body temperature

Summary

Thermoregulation is one of the most vital functions of the brain, but how temperature information is converted into homeostatic responses remains unknown. Here we use an unbiased approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) within the preoptic hypothalamus that orchestrate the homeostatic response to heat. We show that these WSNs are molecularly-defined by co-expression of the neuropeptides BDNF and PACAP. Optical recordings in awake, behaving mice reveal that these neurons are selectively activated by environmental warmth. Optogenetic excitation of WSNs triggers rapid hypothermia, mediated by reciprocal changes in heat production and loss, as well as dramatic cold-seeking behavior. Projection-specific manipulations demonstrate that these distinct effectors are controlled by anatomically segregated pathways. These findings reveal a molecularly-defined cell type that coordinates the diverse behavioral and autonomic responses to heat. Identification of these warm-sensitive cells provides genetic access to the core neural circuit regulating the body temperature of mammals.

Graphical Abstract

eTOC

The body temperature of mammals is tightly regulated, but the identity of the key neurons responsible for thermoregulation has remained elusive. Tan et al use an approach for activity-dependent RNA sequencing to identify warm-sensitive neurons (WSNs) in the preoptic hypothalamus that are activated by ambient heat. Optical stimulation of these WSNs causes body temperature to plummet via coordinated autonomic and behavioral mechanisms. The molecular identification of these WSNs reveals a convergence point for the regulation of body temperature in the brain.