Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
7-29-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-62311-x
PMID
40730814
PMCID
PMC12307685
PubMedCentral® Posted Date
7-29-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount. Sleep-promoting circuits become hyperactive after sleep loss and are associated with increased whole-brain activity. During sleep restriction, optogenetic inhibition of sleep-promoting circuits to reduce sleep drive protects against seizures. Downregulation of the 5HT1A serotonin receptor in sleep-promoting cells mediates the effect of sleep drive on seizures, and we identify an FDA-approved 5HT1A agonist to mitigate seizures. Our findings demonstrate that while homeostatic sleep is needed to recoup lost sleep, sleep drive comes at the cost of increasing seizure susceptibility.
Keywords
Animals, Seizures, Sleep, Sleep Deprivation, Disease Models, Animal, Brain, Drosophila melanogaster, Receptor, Serotonin, 5-HT1A, Optogenetics, Homeostasis, Male, Drosophila Proteins, leep deprivation, Epilepsy
Published Open-Access
yes
Recommended Citation
Cuddapah, Vishnu Anand; Hsu, Cynthia T; Valle Sirias, Fernanda; et al., "Sleep Drive, Not Total Sleep Amount, Increases Seizure Risk" (2025). Duncan NRI Faculty and Staff Publications. 146.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/146
Included in
Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons