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Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice
BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep–wake system may play a role in the reversible loss of consciousness induced by general anesthetics...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580364/ https://www.ncbi.nlm.nih.gov/pubmed/37208941 http://dx.doi.org/10.1111/cns.14267 |
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author | Zhang, Jie Peng, Yiting Liu, Chengxi Zhang, Yu Liang, Xiaoli Yuan, Chengdong Shi, Wenyan Zhang, Yi |
author_facet | Zhang, Jie Peng, Yiting Liu, Chengxi Zhang, Yu Liang, Xiaoli Yuan, Chengdong Shi, Wenyan Zhang, Yi |
author_sort | Zhang, Jie |
collection | PubMed |
description | BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep–wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R‐expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAc(D1R) neurons and the NAc(D1R)‐VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1‐receptor‐expressing neurons located in the nucleus accumbens (NAc(D1R) neurons) and the NAc(D1R)‐VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAc(D1R) neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAc(D1R) neurons and the NAc(D1R)‐VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically‐encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAc(D1R) neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAc(D1R) neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAc(D1R)‐VP pathway exerted opposite effects. CONCLUSION: The NAc(D1R)‐VP pathway serves as a crucial downstream pathway of NAc(D1R) neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells. |
format | Online Article Text |
id | pubmed-10580364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105803642023-10-18 Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice Zhang, Jie Peng, Yiting Liu, Chengxi Zhang, Yu Liang, Xiaoli Yuan, Chengdong Shi, Wenyan Zhang, Yi CNS Neurosci Ther Original Articles BACKGROUND: General anesthesia has long been used in clinical practice, but its precise pharmacological effects on neural circuits are not fully understood. Recent investigations suggest that the sleep–wake system may play a role in the reversible loss of consciousness induced by general anesthetics. Studies in mice have shown that microinjection of dopamine receptor 1 (D1R) agonists into the nucleus accumbens (NAc) promotes recovery from isoflurane anesthesia, while microinjection of D1R antagonists has the opposite effect. Furthermore, during the induction and maintenance of sevoflurane anesthesia, there is a significant decrease in extracellular dopamine levels in the NAc, which subsequently increases during the recovery period. These findings suggest the involvement of the NAc in the regulation of general anesthesia. However, the specific role of D1R‐expressing neurons in the NAc during general anesthesia and the downstream effect pathways are still not well understood. METHODS: In order to analyze the impact of sevoflurane anesthesia on NAc(D1R) neurons and the NAc(D1R)‐VP pathway, this study employed calcium fiber photometry to investigate alterations in the fluorescence intensity of calcium signals in dopamine D1‐receptor‐expressing neurons located in the nucleus accumbens (NAc(D1R) neurons) and the NAc(D1R)‐VP pathway during sevoflurane anesthesia. Subsequently, optogenetic techniques were utilized to activate or inhibit NAc(D1R) neurons and their synaptic terminals in the ventral pallidum (VP), aiming to elucidate the role of NAc(D1R) neurons and the NAc(D1R)‐VP pathway in sevoflurane anesthesia. These experiments were supplemented with electroencephalogram (EEG) recordings and behavioral tests. Lastly, a genetically‐encoded fluorescent sensor was employed to observe changes in extracellular GABA neurotransmitters in the VP during sevoflurane anesthesia. RESULTS: Our findings revealed that sevoflurane administration led to the inhibition of NAc(D1R) neuron population activity, as well as their connections within the ventral pallidum (VP). We also observed a reversible reduction in extracellular GABA levels in the VP during both the induction and emergence phases of sevoflurane anesthesia. Additionally, the optogenetic activation of NAc(D1R) neurons and their synaptic terminals in the VP resulted in a promotion of wakefulness during sevoflurane anesthesia, accompanied by a decrease in EEG slow wave activity and burst suppression rate. Conversely, the optogenetic inhibition of the NAc(D1R)‐VP pathway exerted opposite effects. CONCLUSION: The NAc(D1R)‐VP pathway serves as a crucial downstream pathway of NAc(D1R) neurons, playing a significant role in regulating arousal during sevoflurane anesthesia. Importantly, this pathway appears to be associated with the release of GABA neurotransmitters from VP cells. John Wiley and Sons Inc. 2023-05-19 /pmc/articles/PMC10580364/ /pubmed/37208941 http://dx.doi.org/10.1111/cns.14267 Text en © 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Zhang, Jie Peng, Yiting Liu, Chengxi Zhang, Yu Liang, Xiaoli Yuan, Chengdong Shi, Wenyan Zhang, Yi Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title | Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title_full | Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title_fullStr | Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title_full_unstemmed | Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title_short | Dopamine D1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
title_sort | dopamine d1‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580364/ https://www.ncbi.nlm.nih.gov/pubmed/37208941 http://dx.doi.org/10.1111/cns.14267 |
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