Divergent Neural Activity in the VLPO During Anesthesia and Sleep

Luo, Mingbiao; Ma, Fei‐Xiang; Liu, Xiaotong; Jin, Zikang; Wang, Yingwei; Xu, Min

doi:10.1002/advs.202203395

Cited by 15 publications

(11 citation statements)

References 88 publications

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“…To quantitatively assess brain states during anesthesia, we utilized EEG and electromyography (EMG) recordings. The depth of anesthesia was evaluated based on the power ratio of the EEG signals within the delta (0.5–4 Hz) and theta (6–10 Hz) frequency bands, combined with the changes in the EMG ( Luo et al, 2023 ). Our results indicated that the administration of either KET or ISO elevated the EEG delta/theta power ratio while reducing EMG power ( Figure 1—figure supplement 1 ), suggesting that each drug induced a loss of consciousness.…”

Section: Resultsmentioning

confidence: 99%

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Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

Wang

et al. 2024

eLife

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Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of KET and ISO effects on c-Fos expression across the brain, utilizing principal component analysis (PCA) and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings demonstrate that KET significantly activates cortical and subcortical arousal-promoting nuclei, with the somatosensory cortex (SS) serving as a hub node, corroborating the top-down general anesthesia theory for dissociative anesthesia. In contrast, ISO activates the nuclei in the hypothalamus and brain-stem, with the locus coeruleus (LC) as a hub node, implying a bottom-up mechanism for anesthetic-induced unconsciousness. Notably, the coactivation of sleep-wakefulness regulation, analgesia-related, neuroendocrine-related nuclei (e.g., prelimbic area (PL) and infralimbic areas (ILA), and the anterior paraventricular nucleus (aPVT), Edinger-Westphal nucleus (EW), locus coeruleus (LC), parabrachial nucleus (PB), solitary tract nucleus (NTS)) by both anesthetics underscores shared features such as unconsciousness, analgesia, and autonomic regulation, irrespective of their specific molecular targets. In conclusion, our results emphasize the distinct actions of KET and ISO while also uncovering the commonly activated brain regions, thus contributing to the advancement of our understanding of the mechanisms under-lying general anesthesia.

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Section: Resultsmentioning

confidence: 99%

“…EEG and EMG recordings were conducted as previously described ( Luo et al, 2023 ). Specifically, a stainless-steel electrode was positioned over the frontal cortex for EEG measurements, while an insulated EMG electrode was inserted into the neck muscles.…”

Section: Methodsmentioning

confidence: 99%

Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

Wang

et al. 2024

eLife

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“…To quantitatively assess brain states across the four groups, we utilized electroencephalography (EEG) and electromyography (EMG) recordings (Figure 1—figure supplement 1). The depth of anesthesia was evaluated based on the power ratio of the EEG within the delta (0.5–4 Hz) and theta (6–10 Hz) frequency bands, combined with the changes in the EMG (Luo et al, 2023). Our findings showed that ISO and KET elevated EEG power ratio while reducing EMG power, suggesting both drugs induced a loss of consciousness.…”

Section: Resultsmentioning

confidence: 99%

Comparative Brain-Wide Mapping of Ketamine and Isoflurane-Activated Nuclei and Functional Networks

Wang

et al. 2023

Preprint

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Ketamine (KET) and isoflurane (ISO) are two widely used general anesthetics, yet their distinct and shared neurophysiological mechanisms remain elusive. In this study, we conducted a comparative analysis of KET and ISO effects on c-Fos expression across the brain, utilizing principal component analysis (PCA) and c-Fos-based functional network analysis to evaluate the responses of individual brain regions to each anesthetic. Our findings demonstrate that KET significantly activates cortical and subcortical arousal-promoting nuclei, with the somatosensory cortex (SS) serving as a hub node, corroborating the top-down general anesthesia theory for dissociative anesthesia. In contrast, ISO activates the nuclei in the hypothalamus and brainstem, with the locus coeruleus (LC) as a hub node, implying a bottom-up mechanism for anesthetic-induced unconsciousness. Notably, the coactivation of sleep-wakefulness regulation, analgesia-related, neuroendocrine-related nuclei (e.g., prelimbic area (PL) and infralimbic areas (ILA), and the anterior paraventricular nucleus (aPVT), Edinger-Westphal nucleus (EW), locus coeruleus (LC), parabrachial nucleus (PB), solitary tract nucleus (NTS)) by both anesthetics underscores shared features such as unconsciousness, analgesia, and autonomic regulation, irrespective of their specific molecular targets. In conclusion, our results emphasize the distinct actions of KET and ISO while also uncovering the commonly activated brain regions, thus contributing to the advancement of our understanding of the mechanisms underlying general anesthesia.

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“…All brains were sectioned to verify viral fluorescence expression, and placements of the optical fibers after the experiment was completed. Z‐scores transformed Ca 2+ signals were used to calculate the state of the PVH neurons 16,17 …”

Section: Methodsmentioning

confidence: 99%

Glutamatergic neurons in the paraventricular hypothalamic nucleus regulate isoflurane anesthesia in mice

et al. 2023

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The glutamatergic–mediated excitatory system in the brain is vital for the regulation of sleep–wake and general anesthesia. Specifically, the paraventricular hypothalamic nucleus (PVH), which contains mainly glutamatergic neurons, has been shown to play a critical role in sleep–wake. Here, we sought to explore whether the PVH glutamatergic neurons have an important effect on the process of general anesthesia. We used c‐fos staining and in vivo calcium signal recording to observe the activity changes of the PVH glutamatergic neurons during isoflurane anesthesia and found that both c‐fos expression in the PVH and the calcium activity of PVH glutamatergic neurons decreased in isoflurane anesthesia and significantly increased during the recovery process. Chemogenetic activation of PVH glutamatergic neurons prolonged induction time and shortened emergence time from anesthesia by decreasing the depth of anesthesia. Using chemogenetic inhibition of PVH glutamatergic neurons under isoflurane anesthesia, we found that inhibition of PVH glutamatergic neurons facilitated the induction process and delayed the emergence accompanied by deepening the depth of anesthesia. Together, these results identify a crucial role for PVH glutamatergic neurons in modulating isoflurane anesthesia.

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Divergent Neural Activity in the VLPO During Anesthesia and Sleep

Cited by 15 publications

References 88 publications

Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

Comparative brain-wide mapping of ketamine- and isoflurane-activated nuclei and functional networks in the mouse brain

Comparative Brain-Wide Mapping of Ketamine and Isoflurane-Activated Nuclei and Functional Networks

Glutamatergic neurons in the paraventricular hypothalamic nucleus regulate isoflurane anesthesia in mice

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