Preoptic Neural Circuitry for Dramatic and Gentle Thermoregulation

 Ruiqi Pang1,2 · Haipeng Yu2,3 · Jincheng Wang2  · Zhiyue Shi4  · Huizhong Wen2  · Guangyan Wu5  · Xuan Zhang2  · Yueting Zhang1,2 · Qiaoqian Wei1,2 · Bo Li6  · Xueqing Yi6  · Kai Liu6  · Shaowen Qian6  · Yi Zhou
1 Guangxi Key Laboratory of Special Biomedicine and Advanced Institute for Brain and Intelligence, School of Medicine, Guangxi University, Nanning 530004, China 
2 Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Army Medical University, Chongqing 400038, China 
3 Advanced Institute for Brain and Intelligence, School of Physical Science and Technology, Guangxi University, Nanning 530004, China 
4 Department of Vascular Surgery, Southwest Hospital, Army Medical University, Chongqing 400038, China 
5 Experimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, China 
6 Department of Radiology, The 960th Hospital of Joint Logistics Support Force of PLA (Former Jinan Military General Hospital), Jinan 250031, China

Abstract
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.

Keywords
Ventromedial preoptic area; Ventral part of the lateral preoptic nucleus; Dorsomedial hypothalamus; Brown adipose tissue; Warm defense; Mice