Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, 3616 Trousdale Parkway, AHF-252, Los Angeles, CA 90089-0372, USA.
Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Cell Metab. 2018 Jul 3;28(1):55-68.e7. doi: 10.1016/j.cmet.2018.05.001. Epub 2018 May 31.
Classical mechanisms through which brain-derived molecules influence behavior include neuronal synaptic communication and neuroendocrine signaling. Here we provide evidence for an alternative neural communication mechanism that is relevant for food intake control involving cerebroventricular volume transmission of the neuropeptide melanin-concentrating hormone (MCH). Results reveal that the cerebral ventricles receive input from approximately one-third of MCH-producing neurons. Moreover, MCH cerebrospinal fluid (CSF) levels increase prior to nocturnal feeding and following chemogenetic activation of MCH-producing neurons. Utilizing a dual viral vector approach, additional results reveal that selective activation of putative CSF-projecting MCH neurons increases food intake. In contrast, food intake was reduced following immunosequestration of MCH endogenously present in CSF, indicating that neuropeptide transmission through the cerebral ventricles is a physiologically relevant signaling pathway for energy balance control. Collectively these results suggest that neural-CSF volume transmission signaling may be a common neurobiological mechanism for the control of fundamental behaviors.
经典的脑源性分子影响行为的机制包括神经元突触通讯和神经内分泌信号。在这里，我们提供了一个替代的神经通讯机制的证据，该机制与涉及神经肽黑素浓缩激素（MCH）的脑室内容积传递的食物摄入控制有关。研究结果表明，大脑脑室接收来自大约三分之一的 MCH 产生神经元的输入。此外，MCH 脑脊液（CSF）水平在夜间进食前和化学遗传激活 MCH 产生神经元后增加。利用双病毒载体方法，进一步的结果表明，选择性激活推定的 CSF 投射 MCH 神经元会增加食物摄入。相比之下，MCH 内源性免疫隔离 CSF 会减少食物摄入，表明通过脑室的神经肽传递是能量平衡控制的一种生理相关信号通路。总的来说，这些结果表明，神经-CSF 容积传递信号可能是控制基本行为的共同神经生物学机制。
