Hsu Ted M, Hahn Joel D, Konanur Vaibhav R, Noble Emily E, Suarez Andrea N, Thai Jessica, Nakamoto Emily M, Kanoski Scott E
Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, United States.
Neuroscience Program, University of Southern California, Los Angeles, United States.
Elife. 2015 Dec 15;4:e11190. doi: 10.7554/eLife.11190.
Feeding behavior rarely occurs in direct response to metabolic deficit, yet the overwhelming majority of research on the biology of food intake control has focused on basic metabolic and homeostatic neurobiological substrates. Most animals, including humans, have habitual feeding patterns in which meals are consumed based on learned and/or environmental factors. Here we illuminate a novel neural system regulating higher-order aspects of feeding through which the gut-derived hormone ghrelin communicates with ventral hippocampus (vHP) neurons to stimulate meal-entrained conditioned appetite. Additional results show that the lateral hypothalamus (LHA) is a critical downstream substrate for vHP ghrelin-mediated hyperphagia and that vHP ghrelin activated neurons communicate directly with neurons in the LHA that express the neuropeptide, orexin. Furthermore, activation of downstream orexin-1 receptors is required for vHP ghrelin-mediated hyperphagia. These findings reveal novel neurobiological circuitry regulating appetite through which ghrelin signaling in hippocampal neurons engages LHA orexin signaling.
进食行为很少直接因代谢不足而发生，但绝大多数关于食物摄入控制生物学的研究都集中在基本代谢和稳态神经生物学底物上。包括人类在内的大多数动物都有习惯性进食模式，即根据学习和/或环境因素进食。在这里，我们阐明了一个调节进食高阶方面的新型神经系统，肠道衍生的激素胃饥饿素通过该系统与腹侧海马体（vHP）神经元进行通信，以刺激与进餐相关的条件性食欲。其他结果表明，下丘脑外侧区（LHA）是vHP胃饥饿素介导的摄食过多的关键下游底物，并且vHP胃饥饿素激活的神经元直接与表达神经肽食欲素的LHA神经元进行通信。此外，vHP胃饥饿素介导的摄食过多需要下游食欲素-1受体的激活。这些发现揭示了通过海马神经元中的胃饥饿素信号传导参与LHA食欲素信号传导来调节食欲的新型神经生物学回路。
