Campos Carlos A, Bowen Anna J, Schwartz Michael W, Palmiter Richard D
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Department of Biochemistry, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
Cell Metab. 2016 May 10;23(5):811-20. doi: 10.1016/j.cmet.2016.04.006.
The lateral parabrachial nucleus is a conduit for visceral signals that cause anorexia. We previously identified a subset of neurons located in the external lateral parabrachial nucleus (PBel) that express calcitonin gene-related peptide (CGRP) and inhibit feeding when activated by illness mimetics. We report here that in otherwise normal mice, functional inactivation of CGRP neurons markedly increases meal size, with meal frequency being reduced in a compensatory manner, and renders mice insensitive to the anorexic effects of meal-related satiety peptides. Furthermore, CGRP neurons are directly innervated by orexigenic hypothalamic AgRP neurons, and photostimulation of AgRP fibers supplying the PBel delays satiation by inhibiting CGRP neurons, thereby contributing to AgRP-driven hyperphagia. By establishing a role for CGRP neurons in the control of meal termination and as a downstream mediator of feeding elicited by AgRP neurons, these findings identify a node in which hunger and satiety circuits interact to control feeding behavior.
外侧臂旁核是导致厌食的内脏信号的传导通路。我们之前鉴定出位于外侧臂旁核外部（PBel）的一组神经元，它们表达降钙素基因相关肽（CGRP），并在被疾病模拟物激活时抑制进食。我们在此报告，在其他方面正常的小鼠中，CGRP神经元的功能失活显著增加了每餐食量，餐次频率以补偿方式减少，并且使小鼠对与进餐相关的饱腹感肽的厌食作用不敏感。此外，CGRP神经元直接受下丘脑促食欲的AgRP神经元支配，对供应PBel的AgRP纤维进行光刺激可通过抑制CGRP神经元来延迟饱腹感，从而导致AgRP驱动的摄食过量。通过确立CGRP神经元在控制进餐终止中的作用以及作为AgRP神经元引发的进食的下游介质，这些发现确定了一个饥饿和饱腹感回路相互作用以控制进食行为的节点。
