Department of Biology, Program in Neuroscience, Williams College, Williamstown, MA 01267, USA.
Department of Biology, Program in Neuroscience, Williams College, Williamstown, MA 01267, USA.
Curr Biol. 2018 Dec 3;28(23):3736-3747.e3. doi: 10.1016/j.cub.2018.09.055. Epub 2018 Nov 21.
Eating and sleeping represent two mutually exclusive behaviors that satisfy distinct homeostatic needs. Because an animal cannot eat and sleep at the same time, brain systems that regulate energy homeostasis are likely to influence sleep/wake behavior. Indeed, previous studies indicate that animals adjust sleep cycles around periods of food need and availability. Furthermore, hormones that affect energy homeostasis also affect sleep/wake states: the orexigenic hormone ghrelin promotes wakefulness, and the anorexigenic hormones leptin and insulin increase the duration of slow-wave sleep. However, whether neural populations that regulate feeding can influence sleep/wake states is unknown. The hypothalamic arcuate nucleus contains two neuronal populations that exert opposing effects on energy homeostasis: agouti-related protein (AgRP)-expressing neurons detect caloric need and orchestrate food-seeking behavior, whereas activity in pro-opiomelanocortin (POMC)-expressing neurons induces satiety. We tested the hypotheses that AgRP neurons affect sleep homeostasis by promoting states of wakefulness, whereas POMC neurons promote states of sleep. Indeed, optogenetic or chemogenetic stimulation of AgRP neurons in mice promoted wakefulness while decreasing the quantity and integrity of sleep. Inhibition of AgRP neurons rescued sleep integrity in food-deprived mice, highlighting the physiological importance of AgRP neuron activity for the suppression of sleep by hunger. Conversely, stimulation of POMC neurons promoted sleep states and decreased sleep fragmentation in food-deprived mice. Interestingly, we also found that sleep deprivation attenuated the effects of AgRP neuron activity on food intake and wakefulness. These results indicate that homeostatic feeding neurons can hierarchically affect behavioral outcomes, depending on homeostatic need.
进食和睡眠是两种相互排斥的行为，分别满足不同的体内平衡需求。由于动物不能同时进食和睡眠，因此调节能量体内平衡的大脑系统可能会影响睡眠/觉醒行为。事实上，先前的研究表明，动物会根据食物需求和供应的时间来调整睡眠周期。此外，影响能量体内平衡的激素也会影响睡眠/觉醒状态：食欲激素 ghrelin 促进觉醒，而厌食激素 leptin 和胰岛素则增加慢波睡眠的持续时间。然而，调节进食的神经群体是否会影响睡眠/觉醒状态尚不清楚。下丘脑弓状核包含两种对能量体内平衡产生相反影响的神经元群体：表达 agouti 相关蛋白 (AgRP) 的神经元检测热量需求并协调觅食行为，而表达前阿黑皮素原 (POMC) 的神经元的活动则会引起饱腹感。我们测试了以下假设：AgRP 神经元通过促进觉醒状态来影响睡眠稳态，而 POMC 神经元则促进睡眠状态。事实上，在小鼠中光遗传或化学遗传刺激 AgRP 神经元会促进觉醒，同时减少睡眠的数量和完整性。在饥饿剥夺的小鼠中抑制 AgRP 神经元可恢复睡眠的完整性，突出了 AgRP 神经元活性对饥饿抑制睡眠的生理重要性。相反，刺激 POMC 神经元可促进睡眠状态并减少饥饿剥夺小鼠的睡眠碎片化。有趣的是，我们还发现睡眠剥夺会减弱 AgRP 神经元活性对食物摄入和觉醒的影响。这些结果表明，体内平衡的进食神经元可以根据体内平衡的需求，对行为结果进行层次化影响。
