Preoptic Neural Circuitry for Dramatic and Gentle Thermoregulation

Maintaining a stable body temperature is essential for survival. Multiple brain regions contribute to thermoregulation, but their specific characteristics and underlying neural mechanisms in the coordination of thermoregulation are not fully clarified. Here, we reveal the distinct roles of two preoptic subregions in warm defense in mice: the anterior ventromedial preoptic area (VMPO) and the ventral part of the lateral preoptic nucleus (vLPO). VMPO vesicular glutamate transporter 2​​ (Vglut2) neurons exhibited dramatic responses to rising temperatures, producing a marked decrease in core temperature by warm defense responses. In contrast, excitatory and inhibitory vLPO neurons responded gently to warm stimuli, exerting moderate effects on warm defense. Further postsynaptic tracing and caspase ablation identified distinct cell type-specific downstream targets in the dorsomedial hypothalamus (DMH) mediating these different warm defense responses. Taken together, our findings reveal distinct yet complementary pathways in the preoptic DMH network that enable both rapid and fine-tuned regulation of body temperature under elevated thermal conditions.