Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats

Li, J.; Li, H.; Wang, D.; Guo, Yongxin; Zhang, X.; Ran, Mingzi; Yang, Chunmei; Yang, Qianzi; Dong, Hailong

doi:10.1016/j.bja.2019.07.005

Cited by 51 publications

(49 citation statements)

References 29 publications

(26 reference statements)

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“…Three stainless steel screws were also implanted in the skull at three sites to allow for attachment of EEG electrodes as previously described (Li et al, 2019). Finally, all the screws and fiber were secured to the skull with dental cement.…”

Section: Methodsmentioning

confidence: 99%

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Optogenetic/Chemogenetic Activation of GABAergic Neurons in the Ventral Tegmental Area Facilitates General Anesthesia via Projections to the Lateral Hypothalamus in Mice

Yin

Deng

et al. 2019

Front. Neural Circuits

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The ventral tegmental area (VTA) reportedly regulates sleep and wakefulness through communication with the lateral hypothalamus (LH). It has also been suggested that adequate anesthesia produced by administration of chloral hydrate, ketamine, or halothane significantly reduces the GABAergic neuronal firing rate within the VTA. However, the exact effects on GABAergic neurons in the VTA and the mechanisms through which these neurons modulate anesthesia through associated neural circuits is still unclear. Here, we used optogenetic and chemogenetic methods to specifically activate or inhibit GABAergic neuronal perikarya in the VTA or their projections to the LH in Vgat-Cre mice. Electroencephalogram (EEG) spectral analyses and burst suppression ratio (BSR) calculations were conducted following administration of 0.8 or 1.0% isoflurane, respectively; and loss of righting reflex (LORR), recovery of righting reflex (RORR), and anesthesia sensitivity were assessed under 1.4% isoflurane anesthesia. The results showed that activation of GABAergic neurons in the VTA increased delta wave power from 40.0 to 46.4% (P = 0.006) and decreased gamma wave power from 15.2 to 11.5% (P = 0.017) during anesthesia maintenance. BSR was increased from 51.8 to 68.3% (P = 0.017). Induction time (LORR) was reduced from 333 to 290 s (P = 0.019), whereas arousal time (RORR) was prolonged from 498 to 661 s (P = 0.007). Conversely, inhibition of VTA GABAergic neurons led to opposite effects. In contrast, optical activation of VTA–LH GABAergic projection neurons increased power of slow delta waves from 44.2 to 48.8% (P = 0.014) and decreased that of gamma oscillations from 10.2 to 8.0%. BSR was increased from 39.9 to 60.2% (P = 0.0002). LORR was reduced from 330 to 232 s (P = 0.002), and RORR increased from 396 to 565 s (P = 0.007). Optical inhibition of the projection neurons caused opposite effects in terms of both the EEG spectrum and the BSR, except that inhibition of this projection did not accelerate arousal time. These results indicate that VTA GABAergic neurons could facilitate the anesthetic effects of isoflurane during induction and maintenance while postponing anesthetic recovery, at least partially, through modulation of their projections to the LH.

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Section: Methodsmentioning

confidence: 99%

“…For BSR calculations, EEG data were scored and divided into burst and suppression portions by basic voltage lines (Li et al, 2019). The voltage interval was set according to the amplitude of the suppression waves measured from the mice.…”

Section: Methodsmentioning

confidence: 99%

Optogenetic/Chemogenetic Activation of GABAergic Neurons in the Ventral Tegmental Area Facilitates General Anesthesia via Projections to the Lateral Hypothalamus in Mice

Yin

Deng

et al. 2019

Front. Neural Circuits

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“…Spectrograms were constructed using multitaper methods implemented using the Chronux toolbox in MATLAB 2016a (MathWorks, Cambridge, United States). An improved method for burst suppression rate (BSR, 20 min before cessation of isoflurane) was analysis in MATLAB 2016a (MathWorks, Cambridge, United States) as previous studies (Li et al, 2019;Wang et al, 2020).…”

Section: Eeg Recording and Spectral Analysismentioning

confidence: 99%

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice

Liu

Zhou

et al. 2021

Front. Mol. Neurosci.

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Since their introduction in the 1840s, one of the largest mysteries of modern anesthesia are how general anesthetics create the state of reversible loss of consciousness. Increasing researchers have shown that neural pathways that regulate endogenous sleep–wake systems are also involved in general anesthesia. Recently, the Lateral Habenula (LHb) was considered as a hot spot for both natural sleep–wake and propofol-induced sedation; however, the role of the LHb and related pathways in the isoflurane-induced unconsciousness has yet to be identified. Here, using real-time calcium fiber photometry recordings in vivo, we found that isoflurane reversibly increased the activity of LHb glutamatergic neurons. Then, we selectively ablated LHb glutamatergic neurons in Vglut2-cre mice, which caused a longer induction time and less recovery time along with a decrease in delta-band power in mice under isoflurane anesthesia. Furthermore, using a chemogenetic approach to specifically activate LHb glutamatergic neurons shortened the induction time and prolonged the recovery time in mice under isoflurane anesthesia with an increase in delta-band power. In contrast, chemogenetic inhibition of LHb glutamatergic neurons was very similar to the effects of selective lesions of LHb glutamatergic neurons. Finally, optogenetic activation of LHb glutamatergic neurons or the synaptic terminals of LHb glutamatergic neurons in the rostromedial tegmental nucleus (RMTg) produced a hypnosis-promoting effect in isoflurane anesthesia with an increase in slow wave activity. Our results suggest that LHb glutamatergic neurons and pathway are vital in modulating isoflurane anesthesia.

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“…As a result, investigators are only sampling a restricted range of recovered arousal. For instance, several studies show an increase in the theta/delta ratio [3][4][5]27 , reduced burst suppression ratio 28 , modest behavioral 29 or cortical changes after stimulation 8 . However, they lack the presence of beta and gamma oscillations and purposeful movements characteristic of an awake state in humans 21 or mice 30 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Robust alternative to the righting reflex to assess arousal in rodents

Gao

Calderon

2020

Sci Rep

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The righting reflex (RR) is frequently used to assess level of arousal and applied to animal models of a range of neurological disorders. RR produces a binary result that, when positive, is used to infer restoration of consciousness, often without further behavioral corroboration. We find that RR is an unreliable metric for arousal/recovery of consciousness. Instead, cortical activity and motor behavior that accompany RR are a non-binary, superior criterion that accurately calibrates and establishes level of arousal in rodents.

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Orexin activated emergence from isoflurane anaesthesia involves excitation of ventral tegmental area dopaminergic neurones in rats

Cited by 51 publications

References 29 publications

Optogenetic/Chemogenetic Activation of GABAergic Neurons in the Ventral Tegmental Area Facilitates General Anesthesia via Projections to the Lateral Hypothalamus in Mice

Optogenetic/Chemogenetic Activation of GABAergic Neurons in the Ventral Tegmental Area Facilitates General Anesthesia via Projections to the Lateral Hypothalamus in Mice

Lateral Habenula Glutamatergic Neurons Modulate Isoflurane Anesthesia in Mice

Robust alternative to the righting reflex to assess arousal in rodents

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