Sciolino Natale R, Hsiang Madeline, Mazzone Christopher M, Wilson Leslie R, Plummer Nicholas W, Amin Jaisal, Smith Kathleen G, McGee Christopher A, Fry Sydney A, Yang Cindy X, Powell Jeanne M, Bruchas Michael R, Kravitz Alexxai V, Cushman Jesse D, Krashes Michael J, Cui Guohong, Jensen Patricia
Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
Comparative Medicine, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
Sci Adv. 2022 Aug 19;8(33):eabn9134. doi: 10.1126/sciadv.abn9134.
Recent data demonstrate that noradrenergic neurons of the locus coeruleus (LC-NE) are required for fear-induced suppression of feeding, but the role of endogenous LC-NE activity in natural, homeostatic feeding remains unclear. Here, we found that LC-NE activity was suppressed during food consumption, and the magnitude of this neural response was attenuated as mice consumed more pellets throughout the session, suggesting that LC responses to food are modulated by satiety state. Visual-evoked LC-NE activity was also attenuated in sated mice, suggesting that satiety state modulates LC-NE encoding of multiple behavioral states. We also found that food intake could be attenuated by brief or longer durations of LC-NE activation. Last, we found that activation of the LC to the lateral hypothalamus pathway suppresses feeding and enhances avoidance and anxiety-like responding. Our findings suggest that LC-NE neurons modulate feeding by integrating both external cues (e.g., anxiogenic environmental cues) and internal drives (e.g., satiety).
近期数据表明，蓝斑去甲肾上腺素能神经元（LC-NE）对于恐惧诱导的进食抑制是必需的，但内源性LC-NE活性在自然的稳态进食中的作用仍不清楚。在这里，我们发现进食期间LC-NE活性受到抑制，并且随着小鼠在整个实验过程中消耗更多颗粒，这种神经反应的幅度减弱，这表明LC对食物的反应受饱腹感状态调节。在饱腹的小鼠中，视觉诱发的LC-NE活性也减弱，这表明饱腹感状态调节LC-NE对多种行为状态的编码。我们还发现，短暂或较长时间的LC-NE激活可减弱食物摄入量。最后，我们发现激活从LC到下丘脑外侧的通路会抑制进食，并增强回避和焦虑样反应。我们的研究结果表明，LC-NE神经元通过整合外部线索（例如，产生焦虑的环境线索）和内部驱动力（例如，饱腹感）来调节进食。
