Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Jie, Peng, Yiting, Liu, Chengxi, Zhang, Yu, Liang, Xiaoli, Yuan, Chengdong, Shi, Wenyan, Zhang, Yi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
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
_version_ 1785121928273461248
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
work_keys_str_mv AT zhangjie dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT pengyiting dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT liuchengxi dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT zhangyu dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT liangxiaoli dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT yuanchengdong dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT shiwenyan dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice
AT zhangyi dopamined1receptorexpressingpathwayfromthenucleusaccumbenstoventralpallidummediatedsevofluraneanesthesiainmice