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Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice

Vlasov, Ksenia and Pei, JunZhu and Nehs, Christa J. and Guidera, Jennifer A. and Zhang, Edlyn R. and Kenny, Jonathan D. and Houle, Timothy T. and Brenner, Gary J. and Taylor, Norman E. and Solt, Ken (2021) Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice. Anesthesia and Analgesia, 132 (4). e50-e55. ISSN 0003-2999. https://resolver.caltech.edu/CaltechAUTHORS:20210217-143800779

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1213/ANE.0000000000005387DOIArticle
https://journals.lww.com/anesthesia-analgesia/Abstract/9900/Activation_of_GABAergic_Neurons_in_the.74.aspxPublisherArticle
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.
Funders:
Funding AgencyGrant Number
NIHR01-GM126155
NIHP01-GM118269
James S. McDonnell Foundation220020406
Issue or Number:4
Record Number:CaltechAUTHORS:20210217-143800779
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210217-143800779
Official Citation:Vlasov, Ksenia; Pei, JunZhu; Nehs, Christa J.; Guidera, Jennifer A.; Zhang, Edlyn R.; Kenny, Jonathan D.; Houle, Timothy T.; Brenner, Gary J.; Taylor, Norman E.; Solt, Ken. Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice, Anesthesia & Analgesia. 132(4):e50-e55, April 2021; DOI: 10.1213/ANE.0000000000005387
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:108095
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:18 Feb 2021 17:32
Last Modified:24 Mar 2021 22:43

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