ARC→MeA 投射的激活减少食物摄入。
Activation of the ARC→MeA Projection Reduces Food Intake.
机构信息
The Fleischer Institute for Diabetes and Metabolism, Bronx, NY, United States.
Division of Endocrinology, Department of Medicine, Bronx, NY, United States.
出版信息
Front Neural Circuits. 2020 Nov 5;14:595783. doi: 10.3389/fncir.2020.595783. eCollection 2020.
Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) plays an essential role in the control of food intake and energy expenditure. Melanocortin-4 receptors (MC4Rs) are expressed in key areas that are implicated in regulating energy homeostasis. Although the importance of MC4Rs in the paraventricular hypothalamus (PVH) has been well documented, the role of MC4Rs in the medial amygdala (MeA) on feeding remains controversial. In this study, we specifically examine the role of a novel ARC→MeA neural circuit in the regulation of short-term food intake. To map a local melanocortinergic neural circuit, we use monosynaptic anterograde as well as retrograde viral tracers and perform double immunohistochemistry to determine the identity of the neurons receiving synaptic input from POMC neurons in the ARC. To investigate the role of the ARC→MeA projection on feeding, we optogenetically stimulate channelrhodopsin-2 (ChR2)-expressing POMC fibers in the MeA. Anterograde viral tracing studies reveal that ARC POMC neurons send axonal projections to estrogen receptor-α (ER-α)- and MC4R-expressing neurons in the MeA. Retrograde viral tracing experiments show that the neurons projecting to the MeA is located mainly in the lateral part of the ARC. Optogenetic stimulation of the ARC→MeA pathway reduces short-term food intake. This anorectic effect is blocked by treatment with the MC4R antagonist SHU9119. In addition to the melanocortinergic local circuits within the hypothalamus, this extrahypothalamic ARC→MeA neural circuit would play a role in regulating short-term food intake.
弓状核(ARC)中的前阿黑皮素原(POMC)神经元在控制食物摄入和能量消耗方面起着至关重要的作用。黑皮质素-4 受体(MC4Rs)在参与调节能量平衡的关键区域表达。虽然 MC4Rs 在室旁核(PVH)中的重要性已得到充分证明,但 MC4Rs 在中杏仁核(MeA)对进食的作用仍存在争议。在这项研究中,我们专门研究了 ARC→MeA 神经回路在调节短期食物摄入中的作用。为了绘制局部黑素细胞激素神经回路图,我们使用单突触顺行和逆行病毒示踪剂,并进行双重免疫组织化学染色,以确定从 ARC 的 POMC 神经元接收突触输入的神经元的身份。为了研究 ARC→MeA 投射对进食的作用,我们用光遗传学刺激 ChR2 表达的 POMC 纤维在 MeA 中。顺行病毒追踪研究表明,ARC POMC 神经元向 MeA 中的雌激素受体-α(ER-α)和 MC4R 表达神经元发出轴突投射。逆行病毒追踪实验表明,投射到 MeA 的神经元主要位于 ARC 的外侧部分。光遗传刺激 ARC→MeA 通路可减少短期食物摄入。这种厌食作用被 MC4R 拮抗剂 SHU9119 阻断。除了下丘脑内的黑素细胞激素局部回路外,该下丘脑外 ARC→MeA 神经回路在调节短期食物摄入中也发挥作用。