Kosse Christin, Ivanov Jessica, Knight Zachary, Pellegrino Kyle, Friedman Jeffrey
Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA.
Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.
Nature. 2024 Dec;636(8041):151-161. doi: 10.1038/s41586-024-08098-1. Epub 2024 Oct 23.
The brain processes an array of stimuli, enabling the selection of appropriate behavioural responses, but the neural pathways linking interoceptive inputs to outputs for feeding are poorly understood. Here we delineate a subcortical circuit in which brain-derived neurotrophic factor (BDNF)-expressing neurons in the ventromedial hypothalamus (VMH) directly connect interoceptive inputs to motor centres, controlling food consumption and jaw movements. VMH neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas of the jaw. When food is unavailable, VMH inhibition elicits consummatory behaviours directed at inanimate objects such as wooden blocks, and inhibition of perimesencephalic trigeminal area (pMe5) projections evokes rhythmic jaw movements. The activity of these neurons is decreased during food consumption and increases when food is in proximity but not consumed. Activity is also increased in obese animals and after leptin treatment. VMH neurons receive monosynaptic inputs from both agouti-related peptide (AgRP) and proopiomelanocortin neurons in the arcuate nucleus (Arc), and constitutive VMH activation blocks the orexigenic effect of AgRP activation. These data indicate an Arc → VMH → pMe5 circuit that senses the energy state of an animal and regulates consummatory behaviours in a state-dependent manner.
大脑处理一系列刺激,从而能够选择适当的行为反应,但将内感受性输入与进食输出联系起来的神经通路却鲜为人知。在这里,我们描绘了一个皮层下回路,其中腹内侧下丘脑(VMH)中表达脑源性神经营养因子(BDNF)的神经元直接将内感受性输入与运动中枢相连,控制食物消耗和下颌运动。VMH神经元抑制通过投射到下颌运动前区来控制进食的运动序列,从而增加食物摄入量。当没有食物时,VMH抑制会引发针对诸如木块等无生命物体的完成行为,而抑制中脑周围三叉神经区域(pMe5)的投射会引发有节奏的下颌运动。这些神经元的活动在进食期间会降低,而当食物靠近但未被食用时会增加。在肥胖动物和瘦素治疗后,其活动也会增加。VMH神经元从弓状核(Arc)中的刺鼠相关肽(AgRP)神经元和阿黑皮素原神经元接收单突触输入,VMH的组成性激活会阻断AgRP激活的促食欲作用。这些数据表明存在一个Arc→VMH→pMe5回路,该回路可感知动物的能量状态并以状态依赖的方式调节完成行为。