A subcortical feeding circuit linking an interoceptive node to jaw movement

• 成果类型: Article
• 署名作者: Kosse, Christin; Ivanov, Jessica; Knight, Zachary; Pellegrino, Kyle; Friedman, Jeffrey
• 署名单位: Rockefeller University; Howard Hughes Medical Institute; University of California System; University of California San Francisco
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6673
• DOI: 10.1038/s41586-024-08098-1
• 发表日期: 2024-12-05
• 关键词: neurotrophic factor; energy-balance; severe obesity; neurons; bdnf; nucleus; hypothalamus; hyperphagia; activation; expression

摘要

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 understood1-3. 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. VMHBDNF neuron inhibition increases food intake by gating motor sequences of feeding through projections to premotor areas of the jaw. When food is unavailable, VMHBDNF 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. VMHBDNF neurons receive monosynaptic inputs from both agouti-related peptide (AgRP) and proopiomelanocortin neurons in the arcuate nucleus (Arc), and constitutive VMHBDNF activation blocks the orexigenic effect of AgRP activation. These data indicate an Arc -> VMHBDNF -> pMe5 circuit that senses the energy state of an animal and regulates consummatory behaviours in a state-dependent manner. A subcortical circuit that regulates food consumption in mice is described, involving neurons in the ventromedial hypothalamus that are directly linked to motor centres that regulate feeding and jaw movements.