Pth4 neurons define a novel hypothalamic circuit that promotes sleep via brainstem monoaminergic neurons.

ABSTRACT: 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 pth4 but not qrfp. Noradrenergic locus coeruleus (LC) neurons and serotonergic (5HT) raphe nuclei (RNs) in the hindbrain express distinct pth receptors, 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 5HT RNs. Pth4 neuron-induced sleep is also suppressed in serine/

SUBMITTER: Herget U 

PROVIDER: S-EPMC12818467 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature