Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice

Liu, Yanjun; Chen, Bing; Cai, Yirong; Han, Yuan; Xia, Ying; Li, Nanqi; Fan, Bin; Yuan, Tianjie; Gao, Po; Yu, Weifeng; Jiao, Yingfu; Li, Wenxian

doi:10.1093/abbs/gmab056

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…Secondly, the neural mechanisms of propofol-induced anesthesia are various [7], and the molecular mechanism of regulating NAc GABAergic neurons in the brain needs to be further assessed in order to develop safer and more e cient intravenous anesthetics. Thirdly, although intraperitoneal injection is widely used in rodents to observe anesthetic behavior and better regulate the occurrence of the behavior, it is convenient for experimental observation [36,37]; in recent years, caudal vein injection is used to evaluate the complex pharmacokinetics of anesthesia after systemic administration [9].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous investigations have clari ed that multiple brain biochemical targets and neuron projections participated in the concept [6]. Furthermore, propofol anesthesia is intimately linked to the sleep-arousal circuit [2,7], including GABAergic neurons of the tuberomammillary nucleus (TMN) [8], GABAergic neurons of the thalamic reticular nucleus (TRN) [9], and coherent α oscillations engaging thalamus and cortex [10], cholinergic and glutamatergic neurons in the basal forebrain (BF) [11]and others. The nucleus accumbens (NAc), located at the con uence of the basal nucleus and limbic system, is the major structure of the ventral striatum [12].…”

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confidence: 99%

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GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

Yan

Hang

et al. 2023

Mol Neurobiol

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The mechanism by which general anesthetic drugs modify the state of consciousness remains unidenti ed. In essence, the Nucleus Accumbens(NAc)may be directly engaged in the principle of general anesthesia. However, it is uncertain whether NAc GABAergic neurons play a role in the propofol-induced general anesthesia effect. MethodsWe used immuno uorescence and Western blotting to access the activities of NAc GABAergic neurons during propofol anesthesia, and then we utilized chemogenetic and optogenetic methods to investigate the necessity of NAc GABAergic neurons in the change of consciousness. Moreover, we also conducted behavioral tests to analyze anesthetic induction and emergence. ResultsWe found out that c-Fos expression was considerably dropped in NAc GABAergic neurons after propofol injection. Notably, chemically selective stimulation of NAc GABAergic neurons during propofol anesthesia lowered propofol sensitivity, prolonged the induction of propofol anesthesia, and facilitated recovery; the inhibition of NAc GABAergic neurons exerted opposite effects. Furthermore, optogenetic activation of NAc GABAergic neurons promoted emergence whereas the result of optogenetic inhibition was the opposite. ConclusionsOur results demonstrate that NAc GABAergic neurons modulate induction and emergence of propofol anesthesia. | BackgroundGeneral anesthesia is a reversible condition of unconsciousness induced by anesthetic medications, which have been commonly used in clinical surgery for almost two hundred years [1]. Particularly, the mechanism by which general anesthetic drugs unleash the general anesthesia effect and ulteriorly modify the state of consciousness remains unidenti ed [2]. When general anesthetic drugs are applied for operations, patients frequently have adverse reactions such as low blood pressure, respiratory depression, delayed waking, and even death [3]. Additionally, cognitive dysfunction and stress disorder are likely to be continually companied by patients for a long period [4]. Unfortunately, few effective treatments exist for these debilitating illnesses, accounting for the uncertain mechanism of general anesthesia [2]. As a result,

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

Yan

Hang

et al. 2023

Mol Neurobiol

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“…On the other hand, it resulted a prolonged emergence time with the augment of total power percentages of delta waves and the decrease of total power percentages of beta and gamma waves. These results suggest that the lateral habenula glutamatergic neurons or projections to the rostromedial tegmental nucleus is capable of modifying modulate the anesthesia state of isoflurane ( Liu Y. et al, 2021 ).…”

Section: Other Brain Areasmentioning

confidence: 94%

“…On the contrary, chemogenetic inhibition of the lateral habenula glutamatergic neurons induced a longer induction time, and led to a shorter emergence time. Moreover, optogenetic activation of the lateral habenula glutamatergic neurons accelerated the induction process with an increase in delta waves and a decrease in bata and gamma waves, and delayed the emergence time with a complementary increase of delta band and a decrease in gamma band ( Liu Y. et al, 2021 ).…”

Section: Other Brain Areasmentioning

confidence: 99%

Recent advances in neural mechanism of general anesthesia induced unconsciousness: insights from optogenetics and chemogenetics

Gao,

Wang,

Zhang

et al. 2024

Front. Pharmacol.

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For over 170 years, general anesthesia has played a crucial role in clinical practice, yet a comprehensive understanding of the neural mechanisms underlying the induction of unconsciousness by general anesthetics remains elusive. Ongoing research into these mechanisms primarily centers around the brain nuclei and neural circuits associated with sleep-wake. In this context, two sophisticated methodologies, optogenetics and chemogenetics, have emerged as vital tools for recording and modulating the activity of specific neuronal populations or circuits within distinct brain regions. Recent advancements have successfully employed these techniques to investigate the impact of general anesthesia on various brain nuclei and neural pathways. This paper provides an in-depth examination of the use of optogenetic and chemogenetic methodologies in studying the effects of general anesthesia on specific brain nuclei and pathways. Additionally, it discusses in depth the advantages and limitations of these two methodologies, as well as the issues that must be considered for scientific research applications. By shedding light on these facets, this paper serves as a valuable reference for furthering the accurate exploration of the neural mechanisms underlying general anesthesia. It aids researchers and clinicians in effectively evaluating the applicability of these techniques in advancing scientific research and clinical practice.

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“…Previous studies have found that many nuclei involved in regulating sleep-wakefulness are implicated in the loss of consciousness (LOC) induced by general anesthetics. The locus coeruleus, basal forebrain, thalamic reticular nucleus, paraventricular thalamic nucleus, medial septum, and lateral habenula (LHb) are involved in regulating the LOC caused by propofol [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. The LHb, as part of the epithalamus, is mainly composed of glutamatergic neurons [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice

Zhou,

Zhang,

Zhu

et al. 2024

Pharmaceuticals

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General anesthetics were first used over 170 years ago; however, the mechanisms of how general anesthetics induce loss of consciousness (LOC) remain unclear. Ciprofol, a novel intravenous anesthetic, has been developed by incorporating cyclopropyl into the chemical structure of propofol. This modification offers the benefits of rapid onset and minimal injection pain. Recent studies have revealed that the glutamatergic neurons of the lateral habenula (LHb) play a crucial role in modulating the LOC induced by propofol and sevoflurane. Nevertheless, the specific involvement of LHb in the anesthetic effects of ciprofol remains uncertain. Here, using targeted recombination in active populations (TRAP) combined with electroencephalogram/electromyography recordings and the righting reflex behavioral test, our study revealed that intravenous infusion of ciprofol for 1 h could lead to the induction of c-Fos expression in the LHb in mice. The combination of TRAP and gene ablation, aimed at selectively ablating ciprofol-activated neurons in the LHb, has been shown to facilitate the emergence of ciprofol anesthesia and decrease the proportion of delta waves during the emergence phase. Chemogenetic inhibition of these neurons produced a comparable effect, whereas chemogenetic activation resulted in the opposite outcome. Chemogenetic activation of ciprofol-activated neurons in the LHb delays the emergence of anesthesia and induces a deep hypnotic state during the emergence phase. Taken together, our findings suggest that LHb ciprofol-activated neurons modulate the state of consciousness and could potentially be targeted to manipulate consciousness during ciprofol anesthesia.

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Activation of anterior thalamic reticular nucleus GABAergic neurons promotes arousal from propofol anesthesia in mice

Cited by 9 publications

References 32 publications

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

GABAergic Neurons in the Nucleus Accumbens are Involved in the General Anesthesia Effect of Propofol

Recent advances in neural mechanism of general anesthesia induced unconsciousness: insights from optogenetics and chemogenetics

A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice

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