Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep–Wake State: A Decade of Discovery

Bao, Wei-Wei; Jiang, Shan; Qu, Wei‐Min; Li, Wenxian; Huang, Zhi‐Li

doi:10.1124/pharmrev.122.000717

Cited by 35 publications

(9 citation statements)

References 226 publications

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“…The neural networks, involved in the mechanism of general anesthetics and sleep-wake, are comprised of the prefrontal cortex, basal forebrain, brainstem, hypothalamus, and thalamus 32, 33 . Studies have shown that many other brain regions are involved in general anesthesia 34 . For example, activation of glutamatergic parabrachial nucleus neurons accelerates arousal from sevoflurane anesthesia 35 .…”

Section: Discussionmentioning

confidence: 99%

NE contribution to rebooting unconsciousness caused by midazolam

Liu

Shao

et al. 2023

Preprint

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Generation of the unconsciousness associated with arousal during the initial stage of anesthesia by midazolam is critical for general anesthesia, however, the exact mechanism remains unknown. Here, firstly, we found that the destruction of noradrenergic neurons in the locus coeruleus (LCNE) could prolong the emergence time of midazolam-induced anesthesia. Secondly, the same results were found by activation of the noradrenergic pathway between the LC and the ventrolateral preoptic nucleus (VLPO) using optogenetics and chemogenetics approaches, respectively. Thirdly, this effect was mediated by alpha 1 and beta adrenergic receptors rather than alpha2 adrenergic receptors in the VLPO. Moreover, the noradrenergic pathway to modulate the arousal between the LC and VLPO was controlled by GABAA receptors in the LC and VLPO in our models. Our data demonstrate that activation of the NEergic pathway between the LC and VLPO can promote arousal to prevent delayed recovery from midazolam-induced anesthesia.

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Section: Discussionmentioning

confidence: 99%

NE contribution to rebooting unconsciousness caused by midazolam

Liu

Shao

et al. 2023

Preprint

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“…Modulation of the AAN by anaesthetics has been mainly studied in animal models. 49 It is still unknown whether the alterations of consciousness by anaesthetics are attributable to changes in cortical arousal after a direct effect on the AAN, or whether these are secondary to initial cortical effects. Propofol, sevoflurane, and xenon reproducibly decrease the activity of the thalamus and of the AAN, 50 whereas halothane causes locus coeruleus hyperpolarisation.…”

Section: The Regulation Of Wakefulness and The Generation Of A Mental...mentioning

confidence: 99%

The nature of consciousness in anaesthesia

Montupil,

Cardone,

Staquet

et al. 2023

BJA Open

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“…Considering the similarities between general anesthesia and sleep, recent studies have focused on the sleep–wake systems. Many brain structures related to the sleep–wake cycles have been found to participate in the regulation of general anesthesia ( Bao et al, 2023 ), such as the basal forebrain (BF; L. Wang et al, 2021 ), lateral hypothalamus (LH; Herrera et al, 2016 ), and parabrachial nucleus (PBN; T.X. Wang et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Facilitation of Behavioral and Cortical Emergence from Isoflurane Anesthesia by GABAergic Neurons in Basal Forebrain

Cai

Zhang

et al. 2023

J. Neurosci.

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General anesthesia shares many similarities with natural sleep in behavior and electroencephalogram (EEG) patterns. The latest evidence suggests that general anesthesia and sleep–wake behavior may share overlapping neural substrates. The GABAergic neurons in the basal forebrain (BF) have recently been demonstrated to play a key role in controlling wakefulness. It was hypothesized that BF GABAergic neurons may participate in the regulation of general anesthesia. Here, usingin vivofiber photometry, we found that the activity of BF GABAergic neurons was generally inhibited during isoflurane anesthesia, having obviously decreased during the induction of anesthesia and being gradually restored during the emergence from anesthesia, in Vgat-Cre mice of both sexes. Activation of BF GABAergic neurons with chemogenetic and optogenetic approaches decreased sensitivity to isoflurane, delayed induction, and accelerated emergence from isoflurane anesthesia. Optogenetic activation of BF GABAergic neurons decreased EEG delta power and the burst suppression ratio (BSR) during 0.8% and 1.4% isoflurane anesthesia, respectively. Similar to the effects of activating BF GABAergic cell bodies, photostimulation of BF GABAergic terminals in the thalamic reticular nucleus (TRN) also strongly promoted cortical activation and behavioral emergence from isoflurane anesthesia. Collectively, these results showed that the GABAergic BF is a key neural substrate for general anesthesia regulation that facilitates behavioral and cortical emergence from general anesthesia via the GABAergic BF-TRN pathway. Our findings may provide a new target for attenuating the depth of anesthesia and accelerating emergence from general anesthesia.Statement of Significance:The basal forebrain (BF) is a key brain region controlling sleep–wake behavior. Activation of GABAergic neurons in the BF potently promotes behavioral arousal and cortical activity. Recently, many sleep–wake-related brain structures have been reported to participate in the regulation of general anesthesia. However, it is still unclear what role BF GABAergic neurons play in general anesthesia. In this study, we aim to reveal the role of BF GABAergic neurons in behavioral and cortical emergence from isoflurane anesthesia and elucidate the underlying neural pathways. Understanding the specific role of BF GABAergic neurons in isoflurane anesthesia would improve our understanding of the mechanisms of general anesthesia and may provide a new strategy of accelerating emergence from general anesthesia.

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Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep–Wake State: A Decade of Discovery

Cited by 35 publications

References 226 publications

NE contribution to rebooting unconsciousness caused by midazolam

NE contribution to rebooting unconsciousness caused by midazolam

The nature of consciousness in anaesthesia

Facilitation of Behavioral and Cortical Emergence from Isoflurane Anesthesia by GABAergic Neurons in Basal Forebrain

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