The Somatostatin Pathway Projected from the Basal Forebrain to the Lateral Habenula Promotes Isoflurane Anesthesia Recovery.
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| Titel: | The Somatostatin Pathway Projected from the Basal Forebrain to the Lateral Habenula Promotes Isoflurane Anesthesia Recovery. |
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| Autoren: | Wang Y; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Wang Z; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Xu M; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Wang J; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Cai S; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Zheng D; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Tang A; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Yu T; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Wang Y; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Luo T; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China 407542949@qq.com yusy@zmu.edu.cn yushouyang@foxmail.com.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China., Yu S; Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China 407542949@qq.com yusy@zmu.edu.cn yushouyang@foxmail.com.; Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi 563000, China.; Key Laboratory of Brain Science, Zunyi Medical University, Zunyi 563000, China. |
| Quelle: | The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2025 Oct 01; Vol. 45 (40). Date of Electronic Publication: 2025 Oct 01. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE |
| Imprint Name(s): | Publication: Washington, DC : Society for Neuroscience Original Publication: [Baltimore, Md.] : The Society, c1981- |
| MeSH-Schlagworte: | Isoflurane*/pharmacology , Habenula*/drug effects , Habenula*/physiology , Basal Forebrain*/drug effects , Basal Forebrain*/physiology , Anesthetics, Inhalation*/pharmacology , Somatostatin*/metabolism , Somatostatin*/physiology , Anesthesia Recovery Period*, Animals ; Male ; Mice ; Neural Pathways/physiology ; Neural Pathways/drug effects ; Optogenetics ; Mice, Inbred C57BL ; Mice, Transgenic ; Electroencephalography |
| Abstract: | Competing Interests: The authors declare no competing financial interests. The basal forebrain (BF) acts as a pivotal relay station in the transmission of arousal signals, projecting to both cortical and subcortical structures. Among its downstream targets is the lateral habenula (LHb), which recent research has implicated in the modulation of sleep rhythms and in mediating the loss of consciousness associated with anesthetic agents. In our study, we utilized optogenetic manipulation to selectively modulate the BF VGluT2/SOM neuron projection pathway to the LHb, thereby examining its impact on behavioral and electroencephalographic responses to isoflurane anesthesia. Our results demonstrated that in healthy adult male mice, the activation of the BF SOM →LHb projection pathway significantly prolonged the induction time of anesthesia and shortened recovery time, consequently diminishing the anesthetic potency of isoflurane and reducing EEG δ power. In contrast, the inhibition of this pathway yielded the inverse effects. Notably, modulation of the BF VGluT2 →LHb projection pathway did not significantly affect the induction or recovery times of isoflurane anesthesia. Employing optogenetics in conjunction with calcium signal recording, we elucidated that the arousing effect of the BF SOM →LHb pathway is attributable to the enhanced inhibitory action of BF SOM neurons on LHb Glu neurons. This discovery sheds new light on the neural circuits involved in the loss and recovery of consciousness induced by anesthetic drugs, potentially informing future therapeutic strategies. (Copyright © 2025 the authors.) |
| Contributed Indexing: | Keywords: anesthesia; basal forebrain; isoflurane; lateral habenula; pathway; somatostatin |
| Substance Nomenclature: | CYS9AKD70P (Isoflurane) 0 (Anesthetics, Inhalation) 51110-01-1 (Somatostatin) |
| Entry Date(s): | Date Created: 20250826 Date Completed: 20251001 Latest Revision: 20251005 |
| Update Code: | 20251005 |
| PubMed Central ID: | PMC12491770 |
| DOI: | 10.1523/JNEUROSCI.1316-24.2025 |
| PMID: | 40858501 |
| Datenbank: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Competing Interests: The authors declare no competing financial interests.<br />The basal forebrain (BF) acts as a pivotal relay station in the transmission of arousal signals, projecting to both cortical and subcortical structures. Among its downstream targets is the lateral habenula (LHb), which recent research has implicated in the modulation of sleep rhythms and in mediating the loss of consciousness associated with anesthetic agents. In our study, we utilized optogenetic manipulation to selectively modulate the BF <sup>VGluT2/SOM</sup> neuron projection pathway to the LHb, thereby examining its impact on behavioral and electroencephalographic responses to isoflurane anesthesia. Our results demonstrated that in healthy adult male mice, the activation of the BF <sup>SOM</sup> →LHb projection pathway significantly prolonged the induction time of anesthesia and shortened recovery time, consequently diminishing the anesthetic potency of isoflurane and reducing EEG δ power. In contrast, the inhibition of this pathway yielded the inverse effects. Notably, modulation of the BF <sup>VGluT2</sup> →LHb projection pathway did not significantly affect the induction or recovery times of isoflurane anesthesia. Employing optogenetics in conjunction with calcium signal recording, we elucidated that the arousing effect of the BF <sup>SOM</sup> →LHb pathway is attributable to the enhanced inhibitory action of BF <sup>SOM</sup> neurons on LHb <sup>Glu</sup> neurons. This discovery sheds new light on the neural circuits involved in the loss and recovery of consciousness induced by anesthetic drugs, potentially informing future therapeutic strategies.<br /> (Copyright © 2025 the authors.) |
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| ISSN: | 1529-2401 |
| DOI: | 10.1523/JNEUROSCI.1316-24.2025 |