Work

Sleep drive, not total sleep amount, increases seizure risk

Year: 2025

Type: article

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.

Source: Nature Communications

DOI: 10.1038/s41467-025-62311-x

Authors: Vishnu Anand Cuddapah, Cynthia T. Hsu, Fernanda Valle Sirias, Yongjun Li, Hrishit M. Shah, Christopher Saul, Samantha Killiany, Camilo Guevara, Joy Shon, Zhifeng Yue, Gabrielle L. Gionet, Mary E. Putt, Amita Sehgal

Institutions: Baylor College of Medicine, Texas Children's Hospital, Howard Hughes Medical Institute, California State University, Fresno, University of Pennsylvania, University of Delaware, Children's Hospital of Philadelphia

Language: English

Topic: Sleep and Wakefulness Research

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Citizens United for Research in Epilepsy, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Awards: Balance of sleep and circadian metabolic switches in Drosophila, G4472187405, G5627290623, Interaction between circadian and sleep circuits, The Intellectual and Developmental Disabilities Research Center (IDDRC) at CHOP/Penn, Training Program in Neurodevelopmental Disabilities, Regulation of seizure timing by circadian rhythms and sleep, The Penn-StARR Program for Research in Residency

OpenAlex ID: W4412722631

FWCI: 3.383

Cites: 59

Cited by: 10

Related to: 10