PUBLICATION
Pth4 neurons define a novel hypothalamic circuit that promotes sleep via brainstem monoaminergic neurons
- Authors
- Herget, U., Tran, S., Singh, C., Oikonomou, G., Ryu, S., Rotllant, J., Prober, D.A.
- ID
- ZDB-PUB-251218-10
- Date
- 2025
- Source
- Current biology : CB : (Journal)
- Registered Authors
- Herget, Ulrich, Prober, David, Rotllant, Josep, Ryu, Soojin
- Keywords
- Pth4, QRFP, arousal, locus coeruleus, raphe, sleep, stk32a, zebrafish
- MeSH Terms
-
- Animals
- Brain Stem*/physiology
- Hypothalamus*/physiology
- Neurons*/metabolism
- Neurons*/physiology
- Parathyroid Hormone*/genetics
- Parathyroid Hormone*/metabolism
- Sleep*/physiology
- Zebrafish*/genetics
- Zebrafish*/physiology
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41406966 Full text @ Curr. Biol.
Citation
Herget, U., Tran, S., Singh, C., Oikonomou, G., Ryu, S., Rotllant, J., Prober, D.A. (2025) Pth4 neurons define a novel hypothalamic circuit that promotes sleep via brainstem monoaminergic neurons. Current biology : CB. :.
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 RN. Pth4 neuron-induced sleep is also suppressed in serine/threonine kinase 32a (stk32a) mutants, possibly via stk32a-expressing neurons in the prethalamus that express pth receptors. 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping