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Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats
Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Lippincott Williams & Wilkin
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093725/ https://www.ncbi.nlm.nih.gov/pubmed/34928887 http://dx.doi.org/10.1213/ANE.0000000000005835 |
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author | Brito, Michael A. Li, Duan Fields, Christopher W. Rybicki-Kler, Chloe Dean, Jon G. Liu, Tiecheng Mashour, George A. Pal, Dinesh |
author_facet | Brito, Michael A. Li, Duan Fields, Christopher W. Rybicki-Kler, Chloe Dean, Jon G. Liu, Tiecheng Mashour, George A. Pal, Dinesh |
author_sort | Brito, Michael A. |
collection | PubMed |
description | Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide. METHODS: Under isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5–175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide–induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine. RESULTS: Subanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5–175 Hz; P < .001) and high gamma frontoparietal connectivity (125–175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity (P < .05) and high gamma connectivity (P < .001), which was accompanied by increases (P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity (P < .001), and comparatively weaker frontoparietal high gamma connectivity (P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, P < .001; parietal: CW r[144] = 0.42, P < .001) and nitrous oxide (prefrontal: CW r[156] = 0.46, P < .001; parietal: CW r[156] = 0.56, P < .001) cohorts. CONCLUSIONS: These data bridge changes in cortical acetylcholine with concurrent changes in neurophysiologic complexity, frontoparietal connectivity, and the level of consciousness. |
format | Online Article Text |
id | pubmed-9093725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkin |
record_format | MEDLINE/PubMed |
spelling | pubmed-90937252022-05-16 Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats Brito, Michael A. Li, Duan Fields, Christopher W. Rybicki-Kler, Chloe Dean, Jon G. Liu, Tiecheng Mashour, George A. Pal, Dinesh Anesth Analg Featured Articles Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide. METHODS: Under isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5–175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide–induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine. RESULTS: Subanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5–175 Hz; P < .001) and high gamma frontoparietal connectivity (125–175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity (P < .05) and high gamma connectivity (P < .001), which was accompanied by increases (P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity (P < .001), and comparatively weaker frontoparietal high gamma connectivity (P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, P < .001; parietal: CW r[144] = 0.42, P < .001) and nitrous oxide (prefrontal: CW r[156] = 0.46, P < .001; parietal: CW r[156] = 0.56, P < .001) cohorts. CONCLUSIONS: These data bridge changes in cortical acetylcholine with concurrent changes in neurophysiologic complexity, frontoparietal connectivity, and the level of consciousness. Lippincott Williams & Wilkin 2021-12-20 2022-06 /pmc/articles/PMC9093725/ /pubmed/34928887 http://dx.doi.org/10.1213/ANE.0000000000005835 Text en Copyright © 2021 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 Brito, Michael A. Li, Duan Fields, Christopher W. Rybicki-Kler, Chloe Dean, Jon G. Liu, Tiecheng Mashour, George A. Pal, Dinesh Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title | Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title_full | Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title_fullStr | Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title_full_unstemmed | Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title_short | Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats |
title_sort | cortical acetylcholine levels correlate with neurophysiologic complexity during subanesthetic ketamine and nitrous oxide exposure in rats |
topic | Featured Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093725/ https://www.ncbi.nlm.nih.gov/pubmed/34928887 http://dx.doi.org/10.1213/ANE.0000000000005835 |
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