Sequential Deactivation Across the Hippocampus‐Thalamus‐mPFC Pathway During Loss of Consciousness DOI Creative Commons

Xiaoai Chen,

Samuel Cramer,

Dennis Chan

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

Abstract How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals the anterior cingulate cortex and whole‐brain functional magnetic resonance imaging (fMRI) are conducted rats exposed to graded propofol, undergoing transition from unconsciousness. The results reveal that upon loss (LOC), there sharp increase low‐frequency power electrophysiological signal. Additionally, fMRI exhibit cascade deactivation across pathway including hippocampus, thalamus, medial prefrontal (mPFC) surrounding moment LOC, followed by broader brain activity during sustained Furthermore, sliding window analysis demonstrates temporary synchrony hippocampus‐thalamus‐mPFC preceding LOC. These data suggest LOC may be triggered sequential activities mPFC, while wide‐spread increases other cortical regions commonly observed anesthesia‐induced unconsciousness consequence, rather than cause Taken together, study identifies neural events unfolding transitions unconsciousness, offering systems‐level mechanisms underpinning

Language: Английский

Neurobiological basis of emergence from anesthesia DOI
Xue‐Jun Song,

Jiang-Jian Hu

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(5), P. 355 - 366

Published: March 14, 2024

Language: Английский

Citations

5
Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice DOI Creative Commons
Wenying Duan,

Kang Peng,

Hui-Min Qin

et al.

British Journal of Anaesthesia, Journal Year: 2023, Volume and Issue: 132(2), P. 334 - 342

Published: Dec. 2, 2023

Language: Английский

Citations

12
Activity of the Sodium Leak Channel Maintains the Excitability of Paraventricular Thalamus Glutamatergic Neurons to Resist Anesthetic Effects of Sevoflurane in Mice DOI
Yujie Wu, Donghang Zhang, Jin Liu

et al.

Anesthesiology, Journal Year: 2024, Volume and Issue: 141(1), P. 56 - 74

Published: April 16, 2024

Background Stimulation of the paraventricular thalamus has been found to enhance anesthesia recovery; however, underlying molecular mechanism by which general anesthetics modulate is unclear. This study aimed test hypothesis that sodium leak channel (NALCN) maintains neuronal activity in resist anesthetic effects sevoflurane mice. Methods Chemogenetic and optogenetic manipulations, vivo multiple-channel recordings, electroencephalogram recordings were used investigate role anesthesia. Virus-mediated knockdown and/or overexpression was applied determine how NALCN influenced excitability glutamatergic neurons under sevoflurane. Viral tracers local field potentials explore downstream pathway. Results Single spikes suppressed recovered during emergence. Optogenetic activation shortened emergence period from anesthesia, while chemogenetic inhibition had opposite effect. Knockdown delayed (recovery time: 24 ± 14 64 19 s, P < 0.001; concentration for recovery righting reflex: 1.13% 0.10% 0.97% 0.13%, 0.01). As expected, produced effects. At circuit level, decreased nucleus accumbens, as indicated potential single accumbens. Additionally, on actions reversed optical stimulation Conclusions Activity Editor’s Perspective What We Already Know about Topic Article Tells Us That Is New

Language: Английский

Citations

4
GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol‐ and isoflurane‐mediated general anesthesia DOI Creative Commons

Rulan Yi,

Shi‐Yu Chen,

Fuwang Zhong

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: June 1, 2024

Abstract Background The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially arousal stage anesthesia (GA). But function GA‐induced loss consciousness (LOC) is little known. thalamic reticular nucleus (TRN) only GABAergic neurons‐composed thalamus, which composed parvalbumin (PV) and somatostatin (SST)‐expressing neurons. anterior sector TRN (aTRN) indicated to participate induction anesthesia, but remain unclear. This study aimed reveal role aTRN propofol isoflurane anesthesia. Methods We first set up c‐Fos straining monitor activity variation PV SST neurons during Subsequently, optogenetic tools were utilized activate elucidate Electroencephalogram (EEG) recordings behavioral tests recorded analyzed. Lastly, chemogenetic activation was applied confirm Results showed that both are activated LOC period Optogenetic promoted delayed recovery (ROC) after meanwhile displayed similar effects. Moreover, resulted accumulated burst suppression ratio (BSR) GA, although they represented different effects on power distribution EEG frequency. Conclusion Our findings play a promoting propofol‐ isoflurane‐mediated GA.

Language: Английский

Citations

4
In Vitro and In Vivo Evaluation of Lactoferrin-Modified Liposomal Etomidate with Enhanced Brain-Targeting Effect for General Anesthesia DOI Creative Commons
Ailing Wu,

Houyin Shi,

Luhan Yang

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 805 - 805

Published: June 14, 2024

Etomidate is a general anesthetic that has shown good hemodynamic stability without significant cardiovascular or respiratory depression. Despite several kinds of dosage forms having been reported for this drug, formulation types are very limited in clinical practice, and brain-targeted formulations central nervous system (CNS) drug have rarely reported. Moreover, studies on the biocompatibility, toxicity, effects etomidate preparations vivo were inadequate. The present study was to develop lactoferrin-modified liposomal (Eto-lip-LF) enhanced distribution brain improved effects. Eto-lip-LF had storage hemocompatibility intravenous injection. Compared with non-lactoferrin-containing liposomes, liposomes notably brain-targeting ability vivo, which probably realized by binding transferrin lactoferrin receptors highly distributed brain. therapeutic index about 25.3, higher than many other anesthetics. compared commercial emulsion, could better achieve rapid onset anesthesia recovery from anesthesia, due delivery above results demonstrated potential become an alternative preparation anesthesia.

Language: Английский

Citations

4
Microglia facilitate and stabilize the response to general anesthesia via modulating the neuronal network in a brain region-specific manner DOI Creative Commons
Yang He,

Taohui Liu,

Quansheng He

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Dec. 12, 2023

General anesthesia leads to a loss of consciousness and an unrousable state in patients. Although general anesthetics are widely used clinical practice, their underlying mechanisms remain elusive. The potential involvement nonneuronal cells is unknown. Microglia important immune the central nervous system (CNS) that play critical roles CNS function dysfunction. We unintentionally observed delayed induction early emergence microglia-depleted mice. found microglial depletion differentially regulates neuronal activities by suppressing network anesthesia-activated brain regions activating emergence-activated regions. Thus, microglia facilitate stabilize status. This influence not mediated dendritic spine plasticity. Instead, it relies on activation P2Y12 subsequent calcium influx, which facilitates response. Together, we elucidate regulatory role anesthesia, extending our knowledge how modulate activities.

Language: Английский

Citations

11
Deciphering Consciousness: The Role of Corticothalamocortical Interactions in General Anesthesia DOI Creative Commons
Yuxi Zhou, Shiqian Huang, Tianhao Zhang

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: 212, P. 107593 - 107593

Published: Jan. 8, 2025

General anesthesia is administered to millions of individuals each year, however, the precise mechanism by which it induces unconsciousness remains unclear. While some theories suggest that shares similarities with natural sleep, targeting sleep-promoting areas and inhibiting arousal nuclei, recent research indicates a more complex process. Emerging evidence highlights critical role corticothalamocortical circuits, are involved in higher cognitive functions, controlling states modulating transitions between different conscious during anesthesia. The administration general anesthetics disrupts connectivity within these resulting reversible state unconsciousness. This review elucidates how impair interactions, thereby affecting flow information across various cortical layers disrupting higher-order functions while preserving basic sensory processing. Additionally, prefrontal cortex regulating through both top-down bottom-up pathways was examined. These findings highlight intricate interplay subcortical networks maintaining restoring consciousness under anesthesia, offering potential therapeutic targets for enhancing management.

Language: Английский

Citations

0
Striatal neurones expressing D1 dopamine receptors modulate consciousness in sevoflurane but not propofol anaesthesia in mice DOI

Kang Zhou,

Zijun Hou,

Xuliang Jiang

et al.

British Journal of Anaesthesia, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Low-intensity transcranial ultrasound stimulation modulates neurovascular coupling in mice under propofol anesthesia DOI

Guang Xiao Cui,

Yi Yuan,

Qiaoxuan Wang

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Activation of Glutamatergic Neurons in the Supramammillary Nucleus Promotes the Recovery of Consciousness under Sevoflurane Anesthesia DOI Creative Commons
Jiayan Li,

Yuanhao Wu,

Yihan Wang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Volatile anesthetics have been widely applied during surgery, but the potential mechanisms by which they influence loss of consciousness (LOC), anesthesia maintenance, and recovery (ROC) from remain largely unknown. Recent studies suggested that anesthesia-induced unconsciousness may be due to specific interactions between neural circuits regulate sleep wakefulness. Supramammillary (SuM) glutamatergic neurons are essential for sleep-wakefulness regulation. However, whether SuM involved in modulation under sevoflurane is unclear. Here, it shown activity decreased prior sevoflurane-induced LOC gradually increased following ROC. Selective lesioning promoted induction delayed emergence sensitivity. In addition, optogenetic stimulation or SuM-MS projection behavioral arousal cortical activation steady-state (SSSA) reduced depth caused burst-suppression conditions. Collectively, these results provide compelling evidence contribute regulating states anesthesia.

Language: Английский

Citations

0