Shrivastava Kuldeep, Athreya Vikshar, Lu Yi, Luis-Islas Jorge, Han Ashley, Kowalski Tess F, Rossi Mark A
Center for NeuroMetabolism, Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA.
Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, 08901, USA.
Nat Commun. 2025 May 14;16(1):4474. doi: 10.1038/s41467-025-59686-2.
Impaired regulation of food intake underlies numerous health problems, including obesity and type 2 diabetes, yet how brain systems controlling reward seeking become dysregulated to promote overeating is unknown. Glutamatergic neurons of the lateral hypothalamic area (LHA) are thought to act as a brake on feeding, which is dysregulated during diet-induced obesity. These neurons receive input from the extended amygdala, including the bed nucleus of the stria terminalis (BNST). However, the circuit mechanisms underlying the ability of this pathway to control feeding behavior and how they contribute to dysregulated eating are unclear. Here, we discover that BNST projections to LHA (BNST→LHA) promote reward seeking in an energy state-dependent manner by combining optogenetics, in vivo multiphoton calcium imaging, and electrophysiology in mice. Synaptic strength and neuronal function within the BNST→LHA pathway are dynamically regulated according to energy state to guide reward seeking. These findings suggest that hormonal factors modulate the function of the BNST→LHA pathway to align food seeking with current energy needs.
食物摄入调节受损是包括肥胖症和2型糖尿病在内的众多健康问题的根源，然而，控制奖赏寻求的脑系统如何失调以促进暴饮暴食尚不清楚。下丘脑外侧区（LHA）的谷氨酸能神经元被认为对进食起到抑制作用，而在饮食诱导的肥胖过程中这种抑制作用会失调。这些神经元接收来自扩展杏仁核的输入，包括终纹床核（BNST）。然而，这条通路控制进食行为的潜在回路机制以及它们如何导致进食失调尚不清楚。在这里，我们通过结合光遗传学、体内多光子钙成像和小鼠电生理学发现，BNST向LHA的投射（BNST→LHA）以能量状态依赖的方式促进奖赏寻求。BNST→LHA通路内的突触强度和神经元功能根据能量状态动态调节，以指导奖赏寻求。这些发现表明，激素因素调节BNST→LHA通路的功能，使食物寻求与当前能量需求相匹配。
