Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats
- University of Virginia, United States
Abstract
Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.
Data availability
All data generated or analysed during this study are included in the manuscript and corresponding data tables. We have also deposited our raw datasets for each figure with Dryad are accessible at the following URL: https://doi.org/10.5061/dryad.zcrjdfncm.
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Data from: Respiratory alkalosis provokes spike-wave discharges in seizure-prone ratsDryad Digital Repository, doi:10.5061/dryad.zcrjdfncm.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01NS099586)
- Mark P Beenhakker
National Institute of Neurological Disorders and Stroke (R56NS099586)
- Mark P Beenhakker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States
Ethics
Animal experimentation: All procedures conformed to the National Institutes of Health Guide for Care and Use ofLaboratory Animals and were approved by the University of Virginia Animal Care and UseCommittee (protocol #3892).
Version history
- Received: August 8, 2021
- Preprint posted: August 15, 2021 (view preprint)
- Accepted: January 3, 2022
- Accepted Manuscript published: January 4, 2022 (version 1)
- Version of Record published: February 21, 2022 (version 2)
Copyright
© 2022, Salvati et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats
eLife 11:e72898.
https://doi.org/10.7554/eLife.72898
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