Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption
Hindbrain Double-Negative Feedback Mediates Palatability-Guided Food and Water Consumption
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DOI：
10.1016/j.cell.2020.07.031
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发表时间：
2020-09-17
期刊：
影响因子：
64.5
通讯作者：
Sternson, Scott M.
中科院分区：
文献类型：
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作者：
Gong, Rong;Xu, Shengjin;Sternson, Scott M.
饥饿和口渴有着不同的目标，但控制着相似的摄食行为，人们对这些行为状态之间共享的神经过程知之甚少。我们确定在蓝斑周围（periLC（VGLUT2）神经元）作为一个多突触会聚节点从单独的能量敏感和水化敏感的细胞群体中的多巴胺能神经元。我们开发了在自由活动的小鼠中进行稳定的后脑钙成像的方法，该方法表明periLC（VGLUT2）神经元被调谐到摄食行为，并且对食物或水的消耗做出类似的反应。PeriLC（VGLUT2）神经元在食用过程中受到适口性和稳态需求的抑制。抑制periLC（VGLUT 2）神经元是有益的，并通过增强可口性和延长摄入持续时间来增加消耗。这些属性包括一个双重负反馈关系，维持食物或水的消耗，而不影响食物或水的寻求。PeriLC（VGLUT 2）神经元是饥饿和口渴之间的枢纽，专门控制食物和水摄入的动机，这是导致享乐性暴饮暴食和肥胖的一个因素。
Hunger and thirst have distinct goals but control similar ingestive behaviors, and little is known about neural processes that are shared between these behavioral states. We identify glutamatergic neurons in the peri-locus coeruleus (periLC(VGLUT2) neurons) as a polysynaptic convergence node from separate energy-sensitive and hydration-sensitive cell populations. We develop methods for stable hindbrain calcium imaging in free-moving mice, which show that periLC(VGLUT2) neurons are tuned to ingestive behaviors and respond similarly to food or water consumption. PeriLC(VGLUT2) neurons are scalably inhibited by palatability and homeostatic need during consumption. Inhibition of periLC(VGLUT2) neurons is rewarding and increases consumption by enhancing palatability and prolonging ingestion duration. These properties comprise a double-negative feedback relationship that sustains food or water consumption without affecting food- or water-seeking. PeriLC(VGLUT2) neurons are a hub between hunger and thirst that specifically controls motivation for food and water ingestion, which is a factor that contributes to hedonic overeating and obesity.