臂旁外侧核
黑素皮质素
弓状核
下丘脑
神经科学
弧(几何)
黑素皮质素4受体
臂旁核
生物
人口
核心
受体
内科学
内分泌学
化学
医学
环境卫生
数学
几何学
作者
Alastair S. Garfield,Chia Li,Joseph C. Madara,Bhavik P. Shah,E.S. Webber,Jennifer S. Steger,John N. Campbell,Оксана Гаврилова,Charlotte E. Lee,David P. Olson,Joel K. Elmquist,Bakhos A. Tannous,Michael J. Krashes,Bradford B. Lowell
摘要
Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVH(MC4R) neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVH(MC4R)→lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVH(MC4R)→LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development.
科研通智能强力驱动
Strongly Powered by AbleSci AI