An international research team has identified a new neuronal circuit that regulates sleep in fish. The finding, made in zebrafish (Danio rerio), describes a brain mechanism that functions as a genuine biological switch capable of triggering sleep when the organism accumulates the need to rest.
The study, published in Current Biology and involving scientists from the Spanish Institute of Marine Research (IIM-CSIC) in collaboration with Stanford University and the Howard Hughes Medical Institute, identifies a specific population of hypothalamic neurons defined by the expression of the genes Qrfp and Pth4, which act as promoters of sleep.
To test their function, the researchers used genetic editing and optogenetic tools – a technique that allows neurons to be activated or inhibited with light after being genetically modified to respond to it – in zebrafish larvae. When these neurons were artificially activated, the animals entered a sleep state. This effect depended directly on the neuropeptide Pth4, confirming its key role in sleep regulation.
The experiments also revealed that this neuronal circuit acts through classical sleep-control centres located in the brainstem, particularly the locus coeruleus, associated with noradrenergic signalling, and the raphe nuclei, which are related to serotonin.
In addition, the identified neurons become particularly active when the fish remains awake for long periods, suggesting they are part of the biological system responsible for measuring the accumulated need for rest and triggering sleep when necessary.
According to the researchers, although humans do not possess exactly the same molecule, this circuit may reflect an evolutionarily ancient mechanism shared across different species. Understanding how it works could open new avenues for studying sleep disorders such as insomnia.
This knowledge could help identify new molecular targets for developing drugs to treat sleep disorders or improve understanding of how the brain regulates sleep–wake cycles.