Cargando…

Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia

Cholinergic stimulation of prefrontal cortex (PFC) can reverse anesthesia. Conversely, inactivation of PFC can delay emergence from anesthesia. PFC receives cholinergic projections from basal forebrain, which contains wake-promoting neurons. However, the role of basal forebrain cholinergic neurons i...

Descripción completa

Detalles Bibliográficos
Autores principales: Dean, Jon G., Fields, Christopher W., Brito, Michael A., Silverstein, Brian H., Rybicki-Kler, Chloe, Fryzel, Anna M., Groenhout, Trent, Liu, Tiecheng, Mashour, George A., Pal, Dinesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkin 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093733/
https://www.ncbi.nlm.nih.gov/pubmed/35436248
http://dx.doi.org/10.1213/ANE.0000000000006011
_version_ 1784705398111993856
author Dean, Jon G.
Fields, Christopher W.
Brito, Michael A.
Silverstein, Brian H.
Rybicki-Kler, Chloe
Fryzel, Anna M.
Groenhout, Trent
Liu, Tiecheng
Mashour, George A.
Pal, Dinesh
author_facet Dean, Jon G.
Fields, Christopher W.
Brito, Michael A.
Silverstein, Brian H.
Rybicki-Kler, Chloe
Fryzel, Anna M.
Groenhout, Trent
Liu, Tiecheng
Mashour, George A.
Pal, Dinesh
author_sort Dean, Jon G.
collection PubMed
description Cholinergic stimulation of prefrontal cortex (PFC) can reverse anesthesia. Conversely, inactivation of PFC can delay emergence from anesthesia. PFC receives cholinergic projections from basal forebrain, which contains wake-promoting neurons. However, the role of basal forebrain cholinergic neurons in arousal from the anesthetized state requires refinement, and it is currently unknown whether the arousal-promoting effect of basal forebrain is mediated through PFC. To address these gaps in knowledge, we implemented a novel approach to the use of chemogenetic stimulation and tested the role of basal forebrain cholinergic neurons in behavioral arousal during sevoflurane anesthesia. Next, we investigated the effect of tetrodotoxin-mediated inactivation of PFC on behavioral arousal produced by electrical stimulation of basal forebrain during sevoflurane anesthesia. METHODS: Adult male and female transgenic rats (Long-Evans-Tg [ChAT-Cre]5.1 Deis; n = 22) were surgically prepared for expression of excitatory hM3D(Gq) receptors or mCherry in basal forebrain cholinergic neurons, and activation of these neurons by local delivery of compound 21, an agonist for hM3D(Gq) receptors. The transgenic rats were fitted with microdialysis probes for agonist delivery into basal forebrain and simultaneous prefrontal acetylcholine measurement. Adult male and female Sprague Dawley rats were surgically prepared for bilateral electrical stimulation of basal forebrain and tetrodotoxin infusion (156 μM and 500 nL) into PFC (n = 9) or bilateral electrical stimulation of piriform cortex (n = 9) as an anatomical control. All rats were implanted with electrodes to monitor the electroencephalogram. Heart and respiration rates were monitored using noninvasive sensors. A 6-point scale was used to score behavioral arousal (0 = no arousal and 5 = return of righting reflex). RESULTS: Compound 21 delivery into basal forebrain of rats with hM3D(Gq) receptors during sevoflurane anesthesia produced increases in arousal score (P < .001; confidence interval [CI], 1.80–4.35), heart rate (P < .001; CI, 36.19–85.32), respiration rate (P < .001; CI, 22.81–58.78), theta/delta ratio (P = .008; CI, 0.028–0.16), and prefrontal acetylcholine (P < .001; CI, 1.73–7.46). Electrical stimulation of basal forebrain also produced increases in arousal score (P < .001; CI, 1.85–4.08), heart rate (P = .018; CI, 9.38–98.04), respiration rate (P < .001; CI, 24.15–53.82), and theta/delta ratio (P = .020; CI, 0.019–0.22), which were attenuated by tetrodotoxin-mediated inactivation of PFC. CONCLUSIONS: This study validates the role of basal forebrain cholinergic neurons in behavioral arousal and demonstrates that the arousal-promoting effects of basal forebrain are mediated in part through PFC.
format Online
Article
Text
id pubmed-9093733
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Lippincott Williams & Wilkin
record_format MEDLINE/PubMed
spelling pubmed-90937332022-05-16 Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia Dean, Jon G. Fields, Christopher W. Brito, Michael A. Silverstein, Brian H. Rybicki-Kler, Chloe Fryzel, Anna M. Groenhout, Trent Liu, Tiecheng Mashour, George A. Pal, Dinesh Anesth Analg Featured Articles Cholinergic stimulation of prefrontal cortex (PFC) can reverse anesthesia. Conversely, inactivation of PFC can delay emergence from anesthesia. PFC receives cholinergic projections from basal forebrain, which contains wake-promoting neurons. However, the role of basal forebrain cholinergic neurons in arousal from the anesthetized state requires refinement, and it is currently unknown whether the arousal-promoting effect of basal forebrain is mediated through PFC. To address these gaps in knowledge, we implemented a novel approach to the use of chemogenetic stimulation and tested the role of basal forebrain cholinergic neurons in behavioral arousal during sevoflurane anesthesia. Next, we investigated the effect of tetrodotoxin-mediated inactivation of PFC on behavioral arousal produced by electrical stimulation of basal forebrain during sevoflurane anesthesia. METHODS: Adult male and female transgenic rats (Long-Evans-Tg [ChAT-Cre]5.1 Deis; n = 22) were surgically prepared for expression of excitatory hM3D(Gq) receptors or mCherry in basal forebrain cholinergic neurons, and activation of these neurons by local delivery of compound 21, an agonist for hM3D(Gq) receptors. The transgenic rats were fitted with microdialysis probes for agonist delivery into basal forebrain and simultaneous prefrontal acetylcholine measurement. Adult male and female Sprague Dawley rats were surgically prepared for bilateral electrical stimulation of basal forebrain and tetrodotoxin infusion (156 μM and 500 nL) into PFC (n = 9) or bilateral electrical stimulation of piriform cortex (n = 9) as an anatomical control. All rats were implanted with electrodes to monitor the electroencephalogram. Heart and respiration rates were monitored using noninvasive sensors. A 6-point scale was used to score behavioral arousal (0 = no arousal and 5 = return of righting reflex). RESULTS: Compound 21 delivery into basal forebrain of rats with hM3D(Gq) receptors during sevoflurane anesthesia produced increases in arousal score (P < .001; confidence interval [CI], 1.80–4.35), heart rate (P < .001; CI, 36.19–85.32), respiration rate (P < .001; CI, 22.81–58.78), theta/delta ratio (P = .008; CI, 0.028–0.16), and prefrontal acetylcholine (P < .001; CI, 1.73–7.46). Electrical stimulation of basal forebrain also produced increases in arousal score (P < .001; CI, 1.85–4.08), heart rate (P = .018; CI, 9.38–98.04), respiration rate (P < .001; CI, 24.15–53.82), and theta/delta ratio (P = .020; CI, 0.019–0.22), which were attenuated by tetrodotoxin-mediated inactivation of PFC. CONCLUSIONS: This study validates the role of basal forebrain cholinergic neurons in behavioral arousal and demonstrates that the arousal-promoting effects of basal forebrain are mediated in part through PFC. Lippincott Williams & Wilkin 2022-04-18 2022-06 /pmc/articles/PMC9093733/ /pubmed/35436248 http://dx.doi.org/10.1213/ANE.0000000000006011 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Anesthesia Research Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Featured Articles
Dean, Jon G.
Fields, Christopher W.
Brito, Michael A.
Silverstein, Brian H.
Rybicki-Kler, Chloe
Fryzel, Anna M.
Groenhout, Trent
Liu, Tiecheng
Mashour, George A.
Pal, Dinesh
Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title_full Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title_fullStr Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title_full_unstemmed Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title_short Inactivation of Prefrontal Cortex Attenuates Behavioral Arousal Induced by Stimulation of Basal Forebrain During Sevoflurane Anesthesia
title_sort inactivation of prefrontal cortex attenuates behavioral arousal induced by stimulation of basal forebrain during sevoflurane anesthesia
topic Featured Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093733/
https://www.ncbi.nlm.nih.gov/pubmed/35436248
http://dx.doi.org/10.1213/ANE.0000000000006011
work_keys_str_mv AT deanjong inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT fieldschristopherw inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT britomichaela inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT silversteinbrianh inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT rybickiklerchloe inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT fryzelannam inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT groenhouttrent inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT liutiecheng inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT mashourgeorgea inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia
AT paldinesh inactivationofprefrontalcortexattenuatesbehavioralarousalinducedbystimulationofbasalforebrainduringsevofluraneanesthesia