Network dynamics of hypothalamic feeding neurons.
Network dynamics of hypothalamic feeding neurons.
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DOI：
10.1073/pnas.2011140118
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发表时间：
2021-04-06
影响因子：
11.1
通讯作者：
Cone RD
中科院分区：
文献类型：
--
作者：
Sweeney P;Chen C;Rajapakse I;Cone RD
表达黑皮质素4受体（MC4R）的室旁核（PVN）神经元整合关于能量可用性的激素和神经元信息，并响应于体重和储存能量的变化而参与控制进食、代谢和神经内分泌功能的神经回路。因此，PVN MC4R神经元的动态活动可以用作体重“设定点”的神经表示。在这里，我们表明，PVN MC4R神经元的活动是双向调节的能量状态的变化，神经元的活动逐渐抑制在禁食和增加响应再喂养。总之，这些发现为理解饥饿和饱腹感如何在参与能量稳态的关键神经元内控制提供了一个框架。黑皮质素4受体（MC4R）的突变导致食欲过盛和肥胖，并且是人类单基因肥胖的最常见原因。临床前啮齿动物研究已经确定，MC4R在控制进食中的关键作用可以部分映射到其在下丘脑室旁核（室旁核[PVN]）中的表达，在那里它调节丘脑神经回路的活动。尽管PVN MC4R神经元在调节进食中起关键作用，但这些细胞的体内神经元活性在很大程度上仍未被研究，并且PVN MC4R神经元的网络活性尚未确定。在这里，我们利用体内单细胞显微内镜和数学方法来确定PVN MC4R神经元的活动和网络动力学响应中央黑皮质素受体的能量状态和药理学操纵的变化。我们确定，PVN MC4R神经元表现出定量和定性的变化，响应禁食和再喂养。用治疗性MC4R激动剂setmelanotide对MC4R的药理学刺激迅速增加基础PVN MC4R活性，而黑皮质素3受体（MC3R）的刺激抑制PVN MC4R活性。最后，我们发现，不同的PVN MC4R神经元系综编码能量不足和能量过剩，能量过剩与增强PVN MC4R神经元内的网络连接。这些发现为深入了解饥饿和能量过剩背后的神经动力学提供了有价值的见解。
Paraventricular nucleus (PVN) neurons expressing the melanocortin 4 receptor (MC4R) integrate hormonal and neuronal information concerning energy availability and engage neural circuitry controlling feeding, metabolism, and neuroendocrine function in response to changes in body weight and stored energy. Thereby, the dynamic activity of PVN MC4R neurons may serve as a neural representation of body weight “set point.” Here, we demonstrate that PVN MC4R neuronal activity is bidirectionally regulated by changes in energy state, as neuronal activity is gradually suppressed during fasting and increased in response to refeeding. Together, these findings provide a framework for understanding how hunger and satiety are controlled within critical neurons involved in energy homeostasis. Mutations in the melanocortin 4 receptor (MC4R) result in hyperphagia and obesity and are the most common cause of monogenic obesity in humans. Preclinical rodent studies have determined that the critical role of the MC4R in controlling feeding can be mapped in part to its expression in the paraventricular nucleus of the hypothalamus (paraventricular nucleus [PVN]), where it regulates the activity of anorexic neural circuits. Despite the critical role of PVN MC4R neurons in regulating feeding, the in vivo neuronal activity of these cells remains largely unstudied, and the network activity of PVN MC4R neurons has not been determined. Here, we utilize in vivo single-cell endomicroscopic and mathematical approaches to determine the activity and network dynamics of PVN MC4R neurons in response to changes in energy state and pharmacological manipulation of central melanocortin receptors. We determine that PVN MC4R neurons exhibit both quantitative and qualitative changes in response to fasting and refeeding. Pharmacological stimulation of MC4R with the therapeutic MC4R agonist setmelanotide rapidly increases basal PVN MC4R activity, while stimulation of melanocortin 3 receptor (MC3R) inhibits PVN MC4R activity. Finally, we find that distinct PVN MC4R neuronal ensembles encode energy deficit and energy surfeit and that energy surfeit is associated with enhanced network connections within PVN MC4R neurons. These findings provide valuable insight into the neural dynamics underlying hunger and energy surfeit.
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影响因子：
13.6
作者：
Ghamari-Langroudi M;Cakir I;Lippert RN;Sweeney P;Litt MJ;Ellacott KLJ;Cone RD
通讯作者：
Cone RD
影响因子：
64.8
作者：
Hainmueller T;Bartos M
通讯作者：
Bartos M
影响因子：
8.1
作者：
Collet TH;Dubern B;Mokrosinski J;Connors H;Keogh JM;Mendes de Oliveira E;Henning E;Poitou-Bernert C;Oppert JM;Tounian P;Marchelli F;Alili R;Le Beyec J;Pépin D;Lacorte JM;Gottesdiener A;Bounds R;Sharma S;Folster C;Henderson B;O'Rahilly S;Stoner E;Gottesdiener K;Panaro BL;Cone RD;Clément K;Farooqi IS;Van der Ploeg LHT
通讯作者：
Van der Ploeg LHT
影响因子：
64.8
作者：
Fan, W;Boston, BA;Cone, RD
通讯作者：
Cone, RD
食物的感官检测快速调节弧形喂食电路。
影响因子：
64.5
作者：
Chen Y;Lin YC;Kuo TW;Knight ZA
通讯作者：
Knight ZA