Department of Medicine Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, 450003, Zhengzhou, Henan, China.
Nat Commun. 2020 Dec 10;11(1):6326. doi: 10.1038/s41467-020-20093-4.
It is well recognized that ventromedial hypothalamus (VMH) serves as a satiety center in the brain. However, the feeding circuit for the VMH regulation of food intake remains to be defined. Here, we combine fiber photometry, chemo/optogenetics, virus-assisted retrograde tracing, ChR2-assisted circuit mapping and behavioral assays to show that selective activation of VMH neurons expressing steroidogenic factor 1 (SF1) rapidly inhibits food intake, VMH SF1 neurons project dense fibers to the paraventricular thalamus (PVT), selective chemo/optogenetic stimulation of the PVT-projecting SF1 neurons or their projections to the PVT inhibits food intake, and chemical genetic inactivation of PVT neurons diminishes SF1 neural inhibition of feeding. We also find that activation of SF1 neurons or their projections to the PVT elicits a flavor aversive effect, and selective optogenetic stimulation of ChR2-expressing SF1 projections to the PVT elicits direct excitatory postsynaptic currents. Together, our data reveal a neural circuit from VMH to PVT that inhibits food intake.
人们普遍认为腹内侧下丘脑（VMH）是大脑中的饱腹感中枢。然而，VMH 调节摄食的进食回路仍有待确定。在这里，我们结合光纤光度测定法、化学/光遗传学、病毒辅助逆行追踪、ChR2 辅助回路映射和行为测定，表明选择性激活表达类固醇生成因子 1（SF1）的 VMH 神经元可迅速抑制摄食，VMH SF1 神经元向室旁核（PVT）投射密集纤维，选择性化学/光遗传学刺激 PVT 投射 SF1 神经元或其投射到 PVT 可抑制摄食，化学遗传失活 PVT 神经元可减弱 SF1 神经对摄食的抑制作用。我们还发现，激活 SF1 神经元或其投射到 PVT 会引发味觉厌恶效应，选择性光遗传学刺激 PVT 投射的 ChR2 表达 SF1 投射会引发直接的兴奋性突触后电流。总的来说，我们的数据揭示了一个从 VMH 到 PVT 的神经回路，它可以抑制摄食。
