Brain areas that influence general anesthesia

Leung, L. Stan; Luo, Tao; Ma, Jingyi; Herrick, Ian

doi:10.1016/j.pneurobio.2014.08.001

Cited by 126Sleep and Wakefulness ResearchAnesthesia and Sedative AgentsAnesthesia and Neurotoxicity Research

Brain areas that influence general anesthesia

Leung, L. Stan, Luo, Tao, Ma, Jingyi, Herrick, Ian·2014·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2014.08.001

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Abstract

This document reviews the literature on local brain manipulation of general anesthesia in animals, focusing on behavioral and electrographic effects related to hypnosis or loss of consciousness. Local inactivation or lesion of wake-active areas, such as locus coeruleus, dorsal raphe, pedunculopontine tegmental nucleus, perifornical area, tuberomammillary nucleus, ventral tegmental area and basal forebrain, enhanced general anesthesia. Anesthesia enhancement was shown as a delayed emergence (recovery of righting reflex) from anesthesia or a decrease in the minimal alveolar concentration that induced loss of righting. Local activation of various wake-active areas, including pontis oralis and centromedial thalamus, promoted behavioral or electrographic arousal during maintained anesthesia and facilitated emergence. Lesion of the sleep-active ventrolateral preoptic area resulted in increased wakefulness and decreased isoflurane sensitivity, but only for 6 days after lesion. Inactivation of any structure within limbic circuits involving the medial septum, hippocampus, nucleus accumbens, ventral pallidum, and ventral tegmental area, amygdala, entorhinal and piriform cortex delayed emergence from anesthesia, and often reduced anesthetic-induced behavioral excitation. In summary, the concept that anesthesia works on the sleep-wake system has received strong support from studies that inactivated/lesioned or activated wake-active areas, and weak support from studies that lesioned sleep-active areas. In addition to the conventional wake-sleep areas, limbic structures such as the medial septum, hippocampus and prefrontal cortex are also involved in the behavioral response to general anesthesia. We suggest that hypnosis during general anesthesia may result from disrupting the wake-active neuronal activities in multiple areas and suppressing an atropine-resistant cortical activation associated with movements.

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Many of these wake-promoting nuclei have been studied as targets of inhibitory effects of general anesthetics.
“Many of these nuclei have been explored as targets of the inhibitory effects of general anesthetics [113]”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [113]

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Clinical pharmacokinetics and pharmacodynamics of propofol
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The (Un)Conscious Mouse as a Model for Human Brain Functions: Key Principles of Anesthesia and Their Impact on Translational Neuroimaging
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The Locus Coeruleus Modulates Intravenous General Anesthesia of Zebrafish via a Cooperative Mechanism
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Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia
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SWCNTs/PEDOT:PSS-Modified Microelectrode Arrays for Dual-Mode Detection of Electrophysiological Signals and Dopamine Concentration in the Striatum under Isoflurane Anesthesia
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Medial Septum Glutamatergic Neurons Control Wakefulness Through a Septo-Hypothalamic Circuit
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Dopaminergic Projections From the Ventral Tegmental Area to the Nucleus Accumbens Modulate Sevoflurane Anesthesia in Mice
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The General Anesthetic Isoflurane Bilaterally Modulates Neuronal Excitability
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Activation of noradrenergic terminals in the reticular thalamus delays arousal from propofol anesthesia in mice
Zhang, Y., Fu, B., Liu, C., Yu, S., Luo, T., Zhang, L., Zhou, W., & Yu, T. (2019) · The FASEB Journal · doi:10.1096/fj.201802164rr · Cited by 44 · see citing works
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Brainstem node for loss of consciousness due to GABAA receptor-active anesthetics
Minert, A., & Devor, M. G. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2015.10.001 · Cited by 41 · see citing works
Combined resting state-fMRI and calcium recordings show stable brain states for task-induced fMRI in mice under combined ISO/MED anesthesia
Pradier, B., Wachsmuth, L., Nagelmann, N., Segelcke, D., Kreitz, S., Heß, A., Pogatzki-Zahn, E. M., & Faber, C. (2021) · NeuroImage · doi:10.1016/j.neuroimage.2021.118626 · Cited by 38 · see citing works
Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations
Voss, L. J., García, P. S., Hentschke, H., & Banks, M. I. (2019) · Anesthesiology · doi:10.1097/aln.0000000000002554 · Cited by 37 · see citing works
Granger Causality of the Electroencephalogram Reveals Abrupt Global Loss of Cortical Information Flow during Propofol-induced Loss of Responsiveness
Pullon, R. M., Yan, L., SLEIGH, J. W., & Warnaby, C. E. (2020) · Anesthesiology · doi:10.1097/aln.0000000000003398 · Cited by 38 · see citing works
Oral Delivered Dexmedetomidine Promotes and Consolidates Non-rapid Eye Movement Sleep via Sleep–Wake Regulation Systems in Mice
Feng, Z.-X., Dong, H., Qu, W., & Zhang, W. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01196 · Cited by 36 · see citing works
Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain
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Renal effects of general anesthesia from old to recent studies
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Dose-dependent effects of isoflurane on regional activity and neural network function: A resting-state fMRI study of 14 rhesus monkeys
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The hippocampus participates in a pharmacological rat model of absence seizures
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Neuroimaging in the Kleine-Levin Syndrome
Engström, M., Latini, F., & Landtblom, A. (2018) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-018-0866-y · Cited by 25 · see citing works
Mesopontine Switch for the Induction of General Anesthesia by Dedicated Neural Pathways
Sukhotinsky, I., Minert, A., Soja, P. J., & Devor, M. G. (2016) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000001489 · Cited by 24 · see citing works
Brain state identification and neuromodulation to promote recovery of consciousness
van der Lande, G., Casas-Torremocha, D., Manasanch, A., Porta, L. D., Gosseries, O., Alnagger, N., Barra, A., Mejías, J. F., Panda, R., Riefolo, F., et al. (2024) · Brain Communications · doi:10.1093/braincomms/fcae362 · Cited by 25 · see citing works
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Medial septum modulates hippocampal gamma activity and prepulse inhibition in an N-methyl-d-aspartate receptor antagonist model of schizophrenia
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Enhanced wakefulness following lesions of a mesopontine locus essential for the induction of general anesthesia
Lanir-Azaria, S., Meiri, G., Avigdor, T., Minert, A., & Devor, M. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.12.035 · Cited by 20 · see citing works
Orexinergic innervations at GABAergic neurons of the lateral habenula mediates the anesthetic potency of sevoflurane
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Effects of isoflurane and ethanol administration on c-Fos immunoreactivity in mice
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Reduced Sensitivity to Anesthetic Agents upon Lesioning the Mesopontine Tegmental Anesthesia Area in Rats Depends on Anesthetic Type
Minert, A., Baron, M. S., & Devor, M. G. (2019) · Anesthesiology · doi:10.1097/aln.0000000000003087 · Cited by 21 · see citing works
Circadian differences in emergence from volatile anaesthesia in mice: involvement of the locus coeruleus noradrenergic system
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Transcranial ultrasound neuromodulation facilitates isoflurane-induced general anesthesia recovery and improves cognition in mice
He, J., Zhu, Y., Wu, C., Wu, J., Chen, Y., Yuan, M., Cheng, Z., Zeng, L., & Ji, X. (2023) · Ultrasonics · doi:10.1016/j.ultras.2023.107132 · Cited by 20 · see citing works
Model of anaesthetic induction by unilateral intracerebral microinjection of GABA ergic agonists
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Inactivation of the Tuberomammillary Nucleus by GABAA Receptor Agonist Promotes Slow Wave Sleep in Freely Moving Rats and Histamine-Treated Rats
Xie, J.-F., Fan, K., Wang, C., Xie, P., Hou, M., Xin, L., Cui, G.-F., Wang, L., Shao, Y.-F., & Hou, Y.-P. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2247-3 · Cited by 20 · see citing works
Nutritional ketosis delays the onset of isoflurane induced anesthesia
Ari, C., Kovács, Z., Murdun, C., Koutnik, A. P., Goldhagen, C. R., Rogers, C. Q., Diamond, D. M., & D’Agostino, D. P. (2018) · BMC Anesthesiology · doi:10.1186/s12871-018-0554-0 · Cited by 19 · see citing works
Identifying c-fos Expression as a Strategy to Investigate the Actions of General Anesthetics on the Central Nervous System
Zhang, D., Liu, J., Zhu, T., & Zhou, C. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210909150200 · Cited by 19 · see citing works
Forebrain Acetylcholine Modulates Isoflurane and Ketamine Anesthesia in Adult Mice
Leung, L.-W. S., Chu, L.-W., Prado, M. A. M., & Prado, V. F. (2021) · Anesthesiology · doi:10.1097/aln.0000000000003713 · Cited by 18 · see citing works
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Tricaine Methanesulfonate (MS222) Has Short-Term Effects on Young Adult Zebrafish (Danio rerio) Working Memory and Cognitive Flexibility, but Not on Aging Fish
Fontana, B. D., Alnassar, N., & Parker, M. O. (2021) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2021.686102 · Cited by 17 · see citing works
Claustrum modulates behavioral sensitivity and EEG activity of propofol anesthesia
Luo, T., Li, L., Li, J., Cai, S., Wang, Y., Zhang, L., Yu, S., & Yu, T. (2022) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14012 · Cited by 16 · see citing works
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GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol
Yan, J., Hang, B.-N., Ma, L., Lin, J.-T., Zhou, Y. X., Jiao, X., Yuan, Y.-X., Shao, K.-J., Zhang, L., Xue, Q., et al. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03445-1 · Cited by 16 · see citing works
Midline thalamic inputs to the amygdala: Ultrastructure and synaptic targets
Amir, A., Paré, J., Smith, Y., & Paré, D. (2018) · The Journal of Comparative Neurology · doi:10.1002/cne.24557 · Cited by 16 · see citing works
Anesthesia and surgery induce a functional decrease in excitatory synaptic transmission in prefrontal cortex neurons, and intraoperative administration of dexmedetomidine does not elicit the synaptic dysfunction
Matsumoto, Y., Fujino, Y., & Furue, H. (2021) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2021.07.065 · Cited by 16 · see citing works
Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice
Xia, J.-M., Fan, B., Yi, X., Ni, W., Zhou, Y., Chen, D., Yi, W.-J., Feng, L., Xia, Y., Li, S., et al. (2023) · Anesthesiology · doi:10.1097/aln.0000000000004798 · Cited by 15 · see citing works
Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice
Liu, Y., Chen, B., Cai, Y., Han, Y., Xia, Y., Li, N., Fan, B., Yuan, T., Jiang, J., Gao, P., et al. (2021) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmab056 · Cited by 15 · see citing works
Paradoxical anesthesia: Sleep-like EEG during anesthesia induced by mesopontine microinjection of GABAergic agents
Avigdor, T., Minert, A., Baron, M. S., & Devor, M. G. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113760 · Cited by 15 · see citing works
Heparin‐Derived Theranostic Nanoprobes Overcome the Blood–Brain Barrier and Target Glioma in Murine Model
Samanta, S., Joncour, V. L., Wegrzyniak, O., Rangasami, V. K., Ali‐Löytty, H., Hong, T., Selvaraju, R. K., Åberg, O., Hilborn, J. G., Laakkonen, P. M., et al. (2022) · Advanced Therapeutics · doi:10.1002/adtp.202200001 · Cited by 15 · see citing works
Dopaminergic System in Promoting Recovery from General Anesthesia
Wang, J., Miao, X., Sun, Y., Li, S., Wu, A., & Wei, C. (2023) · Brain Sciences · doi:10.3390/brainsci13040538 · Cited by 14 · see citing works
A Comparison of Brain-State Dynamics across Common Anesthetic Agents in Male Sprague-Dawley Rats
Ward-Flanagan, R., Lo, A. S., Clement, E., & Dickson, C. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073608 · Cited by 14 · see citing works
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Esketamine Anesthetizes Mice With a Similar Potency to Racemic Ketamine
Ma, X., Peng, J., Chen, Y., Wang, Z., Zhou, Q., Yan, J., & Jiang, H. (2023) · Dose-Response · doi:10.1177/15593258231157563 · Cited by 11 · see citing works
GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol‐ and isoflurane‐mediated general anesthesia
Yi, R., Chen, S., Zhong, F., Luo, D., You, Y., Yu, T., Wang, H., Zhou, L., & Zhang, Y. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14782 · Cited by 9 · see citing works
Behavioral responses following repeated bilateral frontal region closed head impacts and fear conditioning in male and female mice.
Vu, P. A., McNamara, E. H., Liu, J., Tucker, L. B., Fu, A. H., & McCabe, J. (2020) · Brain Research · doi:10.1016/j.brainres.2020.147147 · Cited by 8 · see citing works
Disruption of Hippocampal Multisynaptic Networks by General Anesthetics
Kuo, M., & Leung, L.-W. S. (2017) · Anesthesiology · doi:10.1097/aln.0000000000001861 · Cited by 9 · see citing works
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Ketone supplementation abolished isoflurane anesthesia-induced elevation in blood glucose level and increased recovery time from anesthesia in Wistar Albino Glaxo Rijswijk rats
Kovács, Z., D’Agostino, D. P., & Ari, C. (2023) · BMC Anesthesiology · doi:10.1186/s12871-023-02000-8 · Cited by 9 · see citing works
Dopamine D1 ‐receptor‐expressing pathway from the nucleus accumbens to ventral pallidum‐mediated sevoflurane anesthesia in mice
Zhang, J., Peng, Y., Liu, C., Zhang, Y., Liang, X., Yuan, C., Shi, W., & Zhang, Y. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14267 · Cited by 9 · see citing works
No cognitive processing in the unconscious, anesthetic‐like , state of sleep
Vertes, R. P., & Linley, S. B. (2020) · The Journal of Comparative Neurology · doi:10.1002/cne.24963 · Cited by 9 · see citing works
GABAergic Neurons in the Central Amygdala Promote Emergence from Isoflurane Anesthesia in Mice
Zhang, J., Yao, W., Zhang, L., Li, Z.-S., Gong, X.-T., Duan, L.-L., Huang, Z.-X., Chen, T., Huang, J.-C., Yang, S.-X., et al. (2024) · Anesthesiology · doi:10.1097/aln.0000000000005279 · Cited by 8 · see citing works
Brain areas modulation in consciousness during sevoflurane anesthesia
Jie, L., Cai, H., Chen, Y., & Chen, G. (2022) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2022.1031613 · Cited by 8 · see citing works
An exploratory research report on brain mineralization in postoperative delirium and cognitive decline
Lammers‐Lietz, F., Borchers, F., Feinkohl, I., Hetzer, S., Kanar, Ç., Konietschke, F., Lachmann, G., Chien, C., Spies, C., Winterer, G., et al. (2024) · European Journal of Neuroscience · doi:10.1111/ejn.16282 · Cited by 8 · see citing works
Molecular and cellular targets of GABAergic anesthetics in the mesopontine tegmentum that enable pain-free surgery
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Authors: Leung, L. S., Luo, T., Ma, J., & Herrick, I.
Affiliations: Peking University Shenzhen Hospital (CN)
Western University (CA)
ORCID: Luo, Tao
Ma, Jingyi
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2014-11
Volume: 122
Pages: 24-44
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2014.08.001
OpenAlex: W2001908985
Cited by: 126
References: 283
Citations by year: 2026: 7 · 2025: 7 · 2024: 15 · 2023: 19 · 2022: 9 · 2021: 16 · 2020: 9 · 2019: 13 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 2
FWCI: 0.74
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
Scholarship@Western (Western University) (submittedVersion)
Funders: Canadian Institutes of Health
Natural Sciences and Engineering Research Council of Canada
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords: general anesthesia, emergence from anesthesia, locus coeruleus, dorsal raphe nucleus, pedunculopontine nucleus, perifornical area, tuberomammillary nucleus, ventral tegmental area, basal forebrain, ventrolateral preoptic area, limbic system, medial septum, hippocampus, nucleus accumbens, ventral pallidum, amygdala, prefrontal cortex, anesthetic sensitivity, isoflurane, loss of consciousness, hypnosis, righting reflex, lesion studies, brain activation
MeSH terms: Anesthesia, General, Animals, Brain, Humans, Sleep, Wakefulness, Anesthetics, General

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