Herget Ulrich, Tran Steven, Singh Chanpreet, Oikonomou Grigorios, Ryu Soojin, Rotllant Josep, Prober David A
bioRxiv. 2025 Sep 11:2025.09.09.675233. doi: 10.1101/2025.09.09.675233.
Classical studies identified a critical role for the hypothalamus in regulating sleep and wake states, but few such hypothalamic neuronal populations have been identified. Here we describe a sleep-promoting population of hypothalamic neurons that expresses the neuropeptides QRFP and parathyroid hormone 4 (Pth4) in zebrafish. Optogenetic stimulation of these neurons results in a large increase in sleep that requires but not . Noradrenergic locus coeruleus (LC) neurons and serotonergic raphe neurons (RN) in the hindbrain express distinct , and genetic epistasis and cell ablation experiments revealed that Pth4 neuron-induced sleep is suppressed in mutants that lack noradrenaline in the LC or lack the serotonergic RN. Pth4 neuron-induced sleep is also suppressed in ( ) mutants, possibly via -expressing neurons in the prethalamus that express . These results identify QRFP/Pth4 neurons as a novel hypothalamic sleep-promoting population and support a model in which distinct sleep- and wake-promoting hypothalamic populations act via monoaminergic neurons in the hindbrain to control vigilance state.
经典研究确定了下丘脑在调节睡眠和觉醒状态中起关键作用，但已确定的此类下丘脑神经元群体很少。在这里，我们描述了斑马鱼中一群表达神经肽QRFP和甲状旁腺激素4（Pth4）的促进睡眠的下丘脑神经元。对这些神经元进行光遗传学刺激会导致睡眠大幅增加，这需要 但不需要 。后脑的去甲肾上腺素能蓝斑（LC）神经元和5-羟色胺能中缝神经元（RN）表达不同的 ，遗传上位性和细胞消融实验表明，在LC中缺乏去甲肾上腺素或缺乏5-羟色胺能RN的突变体中，Pth4神经元诱导的睡眠受到抑制。在 （ ）突变体中，Pth4神经元诱导的睡眠也受到抑制，可能是通过丘脑前核中表达 的 表达神经元。这些结果确定QRFP/Pth4神经元是一类新的促进睡眠的下丘脑神经元群体，并支持一种模型，即不同的促进睡眠和觉醒的下丘脑群体通过后脑的单胺能神经元来控制警觉状态。
