Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Nat Metab. 2024 Aug;6(8):1616-1631. doi: 10.1038/s42255-024-01100-0. Epub 2024 Aug 15.
Orchestrating complex behaviors, such as approaching and consuming food, is critical for survival. In addition to hypothalamus neuronal circuits, the nucleus accumbens (NAc) also controls appetite and satiety. However, specific neuronal subtypes of the NAc that are involved and how the humoral and neuronal signals coordinate to regulate feeding remain incompletely understood. Here we decipher the spatial diversity of neuron subtypes of the NAc shell (NAcSh) and define a dopamine receptor D1-expressing and Serpinb2-expressing subtype controlling food consumption in male mice. Chemogenetics and optogenetics-mediated regulation of Serpinb2 neurons bidirectionally regulate food seeking and consumption specifically. Circuitry stimulation reveals that the NAcSh→LH projection controls refeeding and can overcome leptin-mediated feeding suppression. Furthermore, NAcSh Serpinb2 neuron ablation reduces food intake and upregulates energy expenditure, resulting in reduced bodyweight gain. Our study reveals a neural circuit consisting of a molecularly distinct neuronal subtype that bidirectionally regulates energy homeostasis, providing a potential therapeutic target for eating disorders.
协调复杂行为，如接近和摄取食物，对生存至关重要。除了下丘脑神经元回路外，伏隔核（NAc）也控制食欲和饱腹感。然而，参与其中的 NAc 的特定神经元亚型以及体液和神经元信号如何协调来调节进食仍不完全清楚。在这里，我们解析了 NAc 壳（NAcSh）神经元亚型的空间多样性，并定义了一种多巴胺受体 D1 表达和 Serpinb2 表达的亚型，控制雄性小鼠的食物消耗。化学遗传学和光遗传学介导的 Serpinb2 神经元的调节可以双向调节食物寻求和消耗。回路刺激显示，NAcSh→LH 投射控制再进食，并可以克服瘦素介导的进食抑制。此外，NAcSh Serpinb2 神经元消融减少食物摄入并上调能量消耗，导致体重增加减少。我们的研究揭示了一个由分子上不同的神经元亚型组成的神经回路，该回路双向调节能量平衡，为饮食失调提供了一个潜在的治疗靶点。
