Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice
Abstract
Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, but the role of these neurons in modulating consciousness is unknown. In this study, designer receptors exclusively activated by designer drugs (DREADDs) were targeted to RMTg GABAergic neurons of Vgat-ires-Cre mice. DREADDs expression was found in the RMTg and other brainstem regions. Activation of these neurons decreased movement and exploratory behavior, impaired motor coordination, induced electroencephalogram (EEG) oscillations resembling nonrapid eye movement (NREM) sleep without loss of righting and reduced the dose requirement for sevoflurane-induced unconsciousness. These results suggest that GABAergic neurons in the RMTg and other brainstem regions promote sedation and facilitate sevoflurane-induced unconsciousness.
Additional Information
© 2021 International Anesthesia Research Society. Accepted for publication December 2, 2020. Funding: This study was supported by grants R01-GM126155 and P01-GM118269 from the National Institutes of Health, and grant 220020406 from the James S. McDonnell Foundation.Additional details
- Eprint ID
- 108095
- Resolver ID
- CaltechAUTHORS:20210217-143800779
- R01-GM126155
- NIH
- P01-GM118269
- NIH
- 220020406
- James S. McDonnell Foundation
- Created
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2021-02-18Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field