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

HGF Aggravated Periodontitis-Associated Gut Barrier and Microbial Dysfunction: Implications for Oral–Gut Axis Regulation DOI Creative Commons
Zhen Chen, Yang Zhong,

Chen Lu

et al.

Biology, Journal Year: 2025, Volume and Issue: 14(5), P. 496 - 496

Published: May 2, 2025

While periodontitis is increasingly linked to systemic disorders through the oral–gut axis, molecular mediators driving gut microbiota dysbiosis and barrier disruption remain elusive. Hepatocyte growth factor (HGF), a novel regulator of inflammatory bone loss in periodontitis, may serve as critical communicator between oral infection distal intestinal pathology. This study investigates how HGF overexpression modulates microbial ecosystem integrity transgenic model. In this study, we combined 16S rRNA sequencing fecal with comprehensive assessments, including markers (D-lactate, LPS, DAO ELISA), structural (villous morphology), analysis (ZO-1, occludin, NOD2 immunohistochemistry), using HGF-overexpressing (HGF-Tg) mice periodontitis. The results demonstrated that increased permeability context evidenced by elevated serum levels D-lactate LPS compared wild type (WT) mice. addition, villous morphology disorder was observed HGF-Tg also diminished protein level occludin upregulated expression Moreover, exhibited significant microbiota, reduced probiotics (e.g., Faecalibaculum). Notably, enrichment periodontitis-associated pathogens Desulfovibrio Streptococcus) gut. Microbial functions, particularly metabolic pathways, were significantly altered when occurred. Some microorganisms like g_Desulfovibrio play role Overall, our findings position orchestrator crosstalk, where its reshapes ecology toward “leaky gut” phenotype compromise integrity, further deepening understanding axis.

Language: Английский

Citations

0
Recent advances in neural mechanism of general anesthesia induced unconsciousness: insights from optogenetics and chemogenetics DOI Creative Commons

Hui Gao,

Jingyi Wang, Rui Zhang

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

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

Language: Английский

Citations

3
Cerebellar Purkinje cell firing promotes conscious recovery from anesthesia state through coordinating neuronal communications with motor cortex DOI Creative Commons

Jinpiao Zhu,

Chang Chen, Xiaodong Liu

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 14(2), P. 480 - 495

Published: Dec. 5, 2023

Background:The neurobiological basis of gaining consciousness from unconscious state induced by anesthetics remains unknown.This study was designed to investigate the involvement cerebello-thalamus-motor cortical loop mediating transitions loss (LOC) an inhalational anesthetic sevoflurane in mice.Methods: The neural tracing and fMRI together with opto-chemogenetic manipulation were used potential link among brain regions.The fiber photometry calcium neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA) norepinephrine (NE), monitored motor cortex (M1) 5 th lobule cerebellar vermis (5Cb) during unconsciousness after exposure.Cerebellar Purkinje cells optogenetically manipulated their influence on exposure.Results: Activation 5Cb increased Ca 2+ flux M1 CaMKIIα + neurons, but this increment significantly reduced inactivation posterior parafascicular thalamic nucleus.The exhibited concerted flux, GABA release wakefulness, consciousness, burst suppression conscious recovery.Ca Glu M1, not 5Cb, showed a strong synchronization EEG suppression, particularly, gamma-band range.In contrast, Glu, NE oscillations coherent gamma band activity only pre-recovery period.The optogenetic activation facilitated emergence anesthesia while inhibition prolonged time consciousness.Conclusions: Our data indicate that neuronal communication integrated through thalamus promotes recovery which may likely serve as arousal regulation.

Language: Английский

Citations

7
Medial Septal Glutamatergic Neurons Modulate States of Consciousness during Sevoflurane Anesthesia in Mice DOI
Junming Xia, Bingqian Fan,

Xiu‐Wen Yi

et al.

Anesthesiology, Journal Year: 2023, Volume and Issue: 140(1), P. 102 - 115

Published: Oct. 9, 2023

Multiple neural structures involved in maintaining wakefulness have been found to promote arousal from general anesthesia. The medial septum is a critical region that modulates behavior. This study hypothesized glutamatergic neurons the play crucial role regulating states of consciousness during sevoflurane anesthesia.Adult male mice were used this study. effects anesthesia on neuronal activity determined by fiber photometry. Lesions and chemogenetic manipulations altered septal induction, emergence, sensitivity sevoflurane. Optogenetic stimulation was observe acute activation cortical behavioral changes sevoflurane-induced continuous steady state burst suppression state.The authors decreased induction recovered early period emergence. Chemogenetic prolonged time (mean ± SD, hM3Dq-clozapine N-oxide vs. hM3Dq-saline, 297.5 60.1 s 229.4 29.9 s, P < 0.001, n = 11) emergence (53.2 11.8 77.5 33.5 0.025, 11). or inhibition these produced opposite effects. During deep anesthesia-induced state, optogenetic induced emergence.The findings reveal has arousal-promoting mice. prolongs accelerates

Language: Английский

Citations

6
Sodium Leak Channel in Glutamatergic Neurons of the Lateral Parabrachial Nucleus Helps to Maintain Respiratory Frequency Under Sevoflurane Anesthesia DOI

Lin Wu,

Donghang Zhang, Yujie Wu

et al.

Neuroscience Bulletin, Journal Year: 2024, Volume and Issue: 40(8), P. 1127 - 1140

Published: May 20, 2024

Language: Английский

Citations

2
Distinct Neural Mechanisms Between Anesthesia Induction and Emergence: A Narrative Review DOI Creative Commons
Donghang Zhang,

Yiyong Wei

Anesthesia & Analgesia, Journal Year: 2024, Volume and Issue: unknown

Published: June 11, 2024

Anesthesia induction and emergence are critical periods for perioperative safety in the clinic. Traditionally, from general anesthesia has been recognized as a simple inverse process of resulting elimination anesthetics central nervous system. However, accumulated evidence indicated that not mirror-image processes because occurrence hysteresis/neural inertia both animals humans. An increasing number studies have highlighted role orexinergic neurons their involved circuits selective regulation but anesthesia. Moreover, additional brain regions also implicated distinct neural mechanisms emergence, which extends concept anesthetic antiparallel processes. Here, we reviewed current literature summarized regarding differential mechanism modulation will facilitate understanding underlying

Language: Английский

Citations

1
Ketamine and the paradox of anaesthetic state transitions DOI Creative Commons
George A. Mashour

British Journal of Anaesthesia, Journal Year: 2023, Volume and Issue: 132(2), P. 224 - 226

Published: Dec. 13, 2023

Language: Английский

Citations

3
Whole‐brain connectivity to the bed nucleus of the stria terminalis calretinin‐expressing interneurons in male mice DOI Open Access

Ke‐Wei Zhu,

Gui‐Jin Tao,

Zhi‐Li Huang

et al.

European Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 58(3), P. 2807 - 2823

Published: July 15, 2023

Abstract The bed nucleus of the stria terminalis (BNST) is a neuropeptide‐enriched brain region that modulates wide variety emotional behaviours and states, including stress, anxiety, reward social interaction. BNST consists diverse subregions neuronal ensembles; however, because high molecular heterogeneity within neurons, mechanisms through which regulates distinct remain largely unclear. Prior studies have identified calretinin (CR)‐expressing lack neuropeptides. Here, employing virus‐based cell‐type‐specific retrograde anterograde tracing systems, we mapped whole‐brain monosynaptic inputs axonal projections CR‐expressing neurons in male mice. We found received mainly from amygdalopiriform transition area, central amygdala hippocampus moderately medial preoptic basolateral amygdala, paraventricular thalamus lateral hypothalamus. Within BNST, plenty input were primarily located oval interfascicular subregions. Furthermore, numerous boutons observed but not other regions, thus suggesting these are type interneuron. These results will help further elucidate circuits underlying elaborate functions BNST.

Language: Английский

Citations

1
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. 22, 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

1
A Common Neuronal Ensemble in the Lateral Habenula Regulates Ciprofol Anesthesia in Mice DOI Creative Commons

Kang Zhou,

Lin-Chen Zhang,

He Zhu

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(3), P. 363 - 363

Published: March 11, 2024

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

Language: Английский

Citations

0