ZFIN ID: ZDB-PUB-190701-4
The Serotonergic Raphe Promote Sleep in Zebrafish and Mice
Oikonomou, G., Altermatt, M., Zhang, R.W., Coughlin, G.M., Montz, C., Gradinaru, V., Prober, D.A.
Date: 2019
Source: Neuron   103(4): 686-701.e8 (Journal)
Registered Authors: Prober, David
Keywords: 5-HT, arousal, fiber photometry, optogenetics, raphe, serotonin, sleep
MeSH Terms:
  • Animals
  • Arousal/genetics
  • Arousal/physiology
  • Buspirone/pharmacology
  • Circadian Rhythm/physiology
  • Fenclonine/pharmacology
  • Homeostasis
  • Male
  • Mice/physiology*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Optogenetics
  • Quipazine/pharmacology
  • Raphe Nuclei/physiology*
  • Serotonergic Neurons/drug effects
  • Serotonergic Neurons/physiology
  • Serotonin/biosynthesis
  • Serotonin/physiology*
  • Serotonin Antagonists/pharmacology
  • Serotonin Receptor Agonists/pharmacology
  • Sleep/physiology*
  • Sleep Deprivation/genetics
  • Sleep Deprivation/physiopathology
  • Tryptophan Hydroxylase/deficiency
  • Tryptophan Hydroxylase/genetics
  • Wakefulness/genetics
  • Wakefulness/physiology
  • Zebrafish/physiology*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
PubMed: 31248729 Full text @ Neuron
The role of serotonin (5-HT) in sleep is controversial: early studies suggested a sleep-promoting role, but eventually the paradigm shifted toward a wake-promoting function for the serotonergic raphe. Here, we provide evidence from zebrafish and mice that the raphe are critical for the initiation and maintenance of sleep. In zebrafish, genetic ablation of 5-HT production by the raphe reduces sleep, sleep depth, and the homeostatic response to sleep deprivation. Pharmacological inhibition or ablation of the raphe reduces sleep, while optogenetic stimulation increases sleep. Similarly, in mice, ablation of the raphe increases wakefulness and impairs the homeostatic response to sleep deprivation, whereas tonic optogenetic stimulation at a rate similar to baseline activity induces sleep. Interestingly, burst optogenetic stimulation induces wakefulness in accordance with previously described burst activity of the raphe during arousing stimuli. These results indicate that the serotonergic system promotes sleep in both diurnal zebrafish and nocturnal rodents.