Empirical evidence suggests that heat exposure reduces food intake. However, the neurocircuit architecture and the signalling mechanisms that form an associative interface between sensory and metabolic modalities remain unknown, despite primary thermoceptive neurons in the pontine parabrachial nucleus becoming well characterized¹. Tanycytes are a specialized cell type along the wall of the third ventricle² that bidirectionally transport hormones and signalling molecules between the brain’s parenchyma and ventricular system^3,4,5,6,7,8. Here we show that tanycytes are activated upon acute thermal challenge and are necessary to reduce food intake afterwards. Virus-mediated gene manipulation and circuit mapping showed that thermosensing glutamatergic neurons of the parabrachial nucleus innervate tanycytes either directly or through second-order hypothalamic neurons. Heat-dependent Fos expression in tanycytes suggested their ability to produce signalling molecules, including vascular endothelial growth factor A (VEGFA). Instead of discharging VEGFA into the cerebrospinal fluid for a systemic effect, VEGFA was released along the parenchymal processes of tanycytes in the arcuate nucleus. VEGFA then increased the spike threshold of Flt1-expressing dopamine and agouti-related peptide (Agrp)-containing neurons, thus priming net anorexigenic output. Indeed, both acute heat and the chemogenetic activation of glutamatergic parabrachial neurons at thermoneutrality reduced food intake for hours, in a manner that is sensitive to both Vegfa loss-of-function and blockage of vesicle-associated membrane protein 2 (VAMP2)-dependent exocytosis from tanycytes. Overall, we define a multimodal neurocircuit in which tanycytes link parabrachial sensory relay to the long-term enforcement of a metabolic code.

经验证据表明，受热会减少食物摄入量。然而，尽管桥臂旁核中的初级热感受神经元已得到很好的表征，但形成感觉和代谢方式之间关联界面的神经回路结构和信号传导机制仍然未知¹。 Tanycytes 是第三脑室壁上的一种特殊细胞类型²，可在大脑实质和脑室系统之间双向运输激素和信号分子^3,4,5,6,7,8。在这里，我们证明单细胞在急性热挑战时被激活，并且对于随后减少食物摄入是必要的。病毒介导的基因操作和电路图谱表明，臂旁核的热敏谷氨酸能神经元直接或通过二级下丘脑神经元支配单细胞。单细胞中热依赖性Fos表达表明它们具有产生信号分子的能力，包括血管内皮生长因子 A (VEGFA)。 VEGFA 不是将 VEGFA 释放到脑脊液中以产生全身效应，而是沿着弓状核中的单胞实质过程释放。然后，VEGFA 增加了表达Flt1的多巴胺和含有刺豚鼠相关肽 ( Agrp ) 的神经元的尖峰阈值，从而启动了净厌食输出。事实上，急性高温和热中性条件下谷氨酸能臂旁神经元的化学遗传学激活都会在数小时内减少食物摄入量，其方式对Vegfa功能丧失和囊泡相关膜蛋白 2 (VAMP2) 依赖性胞吐作用的阻断敏感来自单细胞。总的来说，我们定义了一种多模式神经回路，其中单细胞将臂旁感觉传递与代谢密码的长期执行联系起来。