气候变化领域集成服务门户(CCPortal): Network dynamics of hypothalamic feeding neurons

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DOI	10.1073/pnas.2011140118
	Network dynamics of hypothalamic feeding neurons
	Sweeney P.; Chen C.; Rajapakse I.; Cone R.D.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Feeding; Melanocortin circuitry; Neural networks; Paraventricular hypothalamus
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179958
作者单位	Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, United States; Department of Mathematics, University of Michigan, Ann Arbor, MI 48109, United States; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI 48109, United States; Department of Computational Medicine and Bioinformatics, Medical School, University of Michigan, Ann Arbor, MI 48109, United States; Department of Molecular and Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Sweeney P.,Chen C.,Rajapakse I.,et al. Network dynamics of hypothalamic feeding neurons[J],2021,118(14).
APA	Sweeney P.,Chen C.,Rajapakse I.,&Cone R.D..(2021).Network dynamics of hypothalamic feeding neurons.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Sweeney P.,et al."Network dynamics of hypothalamic feeding neurons".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).