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^Serpinb2→LH^LepR 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.

协调复杂的行为，例如接近和食用食物，对于生存至关重要。除了下丘脑神经元回路之外，伏隔核（NAc）也控制食欲和饱腹感。然而，所涉及的 NAc 的特定神经元亚型以及体液和神经元信号如何协调以调节进食仍不完全清楚。在这里，我们破译了 NAc 壳 (NAcSh) 神经元亚型的空间多样性，并定义了控制雄性小鼠食物消耗的表达多巴胺受体 D1 和表达Serpinb2 的亚型。 Serpinb2 ⁺神经元的化学遗传学和光遗传学介导的调节专门双向调节食物寻找和消耗。电路刺激表明 NAcSh ^Serpinb2 →LH ^LepR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 ⁺神经元消融可减少食物摄入并上调能量消耗，从而减少体重增加。我们的研究揭示了一种由分子上不同的神经元亚型组成的神经回路，可以双向调节能量稳态，为饮食失调提供了潜在的治疗靶点。