Brainwide genetic capture for conscious state transitions

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Summary Abstract Spatially integrated mechanisms of consciousness are unclear 1,2 . An approach to manipulate brainwide circuits regulating via synthetic central nervous system activation may pave the way for more precise transitions in and reveal underlying mechanisms. Toward this goal, we leverage anesthesia as a tool probe at cellular resolution within intact network. We perform chemogenetic capture 3,4 isoflurane anesthesia-activated circuitry mice —in parallel with electrocorticography 5 , wireless mechano- acoustic recording peripheral physiology 6 behavioral classification 7,8 — describe state altered generated absence an anesthetic agent. define patterns under using brain immediate early gene mapping 9–12 combined high density silicon recordings 13 Our data identify subcortical hotspots neural activity unconsciousness network that is globally characterized by increased functional connectivity driven select nodes. provide technical resources spanning single-cell maps neurophysiologic datasets isoflurane-rendered unconscious state, along further its global cellular-level Together, present foundation future research refine viral-genetic generate conscious transitions, such sleep, stasis, analgesia or anesthesia.

Язык: Английский

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Structural Interactions of Ankyrin B with NrCAM and β2 Spectrin

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 6, 2025

Abstract Ank2 is a high confidence autism spectrum disorder (ASD) gene encoding the spectrin-actin scaffold protein Ankyrin B (AnkB). The 220 kDal isoform of AnkB has multiple functions including developmental spine pruning through L1 family cell adhesion molecules (L1-CAMs) and class 3 Semaphorins on dendrites pyramidal neurons to achieve an appropriate excitatory balance in neocortex. Molecular modeling employing AlphaFold was used predict structure interactions with cytoplasmic domain Neuron-glial Related L1-CAM (NrCAM), β2-Spectrin. validity models assessed by analyzing protein-protein co-immunoprecipitation from HEK293 lysates after mutating key residues predicted impair these associations. Results revealed pocket critical membrane-binding that engages NrCAM at conserved motif FIGQY. Alphafold AnkB/β2-Spectrin complex also identified between spectrin-binding β2-Spectrin repeats 14-15. Selected ASD-linked mutations impact binding or were then assayed for interactions. Maternally inherited ASD missense A368G located R977Q Zu51 subdomain disrupted associations β2-Spectrin, respectively. Moreover, impaired neuronal function Semaphorin 3F-induced mouse cortical neuron cultures. These new findings provide structural insights into L1-CAM/AnkB molecular basis etiology associated mutations.

Язык: Английский

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Neural mechanisms linking sleep disturbances to motor and cognitive impairments in Parkinson’s disease: Evidence from resting-state and task-based fNIRS

Brain Research, Год журнала: 2025, Номер 1860, С. 149681 - 149681

Опубликована: Май 8, 2025

Язык: Английский

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Extrasynaptic GABAA receptors in central medial thalamus mediate anesthesia in rats

European Journal of Pharmacology, Год журнала: 2024, Номер 972, С. 176561 - 176561

Опубликована: Апрель 4, 2024

Язык: Английский

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Large-scale coupling of prefrontal activity patterns as a mechanism for cognitive control in health and disease: evidence from rodent models

Frontiers in Neural Circuits, Год журнала: 2024, Номер 18

Опубликована: Апрель 4, 2024

Cognitive control of behavior is crucial for well-being, as allows subject to adapt changing environments in a goal-directed way. Changes cognitive observed during decline elderly and pathological mental conditions. Therefore, the recovery may provide reliable preventive therapeutic strategy. However, its neural basis not completely understood. supported by prefrontal cortex, structure that integrates relevant information appropriate organization behavior. At neurophysiological level, it suggested local large-scale synchronization oscillatory activity patterns spiking between cortex distributed networks. In this review, we focus mainly on rodent models approaching neuronal origin these patterns, behavioral relevance coordination with brain systems. We also examine relationship role normal Finally, based body evidence, propose common mechanism underlie impaired

Язык: Английский

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The brain in chronic insomnia and anxiety disorder: a combined structural and functional fMRI study

Frontiers in Psychiatry, Год журнала: 2024, Номер 15

Опубликована: Июнь 4, 2024

Background Chronic insomnia disorder (CID) is usually associated with Generalized Anxiety Disorder (GAD), which may change brain structure and function. However, the possible markers, imaging characteristics, pathophysiology are unknown. Objective To look at probable pathogenesis of CID in combination GAD. Methods A total 57 patients concomitant GAD healthy controls (HC) were enrolled. Voxel-based morphometry (VBM) functional connectivity (FC) utilized to measure gray matter volume (GMV) changes. Correlation analysis was identify relationships between changes clinical characteristics. Results Patients had decreased GMV left cerebellum, right cerebellar peduncle, insula; increased FC cerebellum angular gyrus, as well insula anterior cingulate gyrus; several areas, including middle gyrus superior postcentral gyrus. These related data could be used relevant features, better understand etiology. Conclusion The intensity strongly severity anxiety. lower interpreted an characteristic CID. Reduced insula, aberrant function prefrontal lobe, contribute Abnormal patients’ complaints.

Язык: Английский

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Recovery of consciousness after acute brain injury: a narrative review

Journal of Intensive Care, Год журнала: 2024, Номер 12(1)

Опубликована: Сен. 26, 2024

Abstract Background Disorders of consciousness (DoC) are frequently encountered in both, acute and chronic brain injuries. In many countries, early withdrawal life-sustaining treatments is common practice for these patients even though the accuracy predicting recovery debated delayed can be seen. this review, we will discuss theoretical concepts pathophysiology, explore effective strategies management, accurate prediction long-term clinical outcomes. We also address research challenges. Main text DoC characterized by alterations arousal and/or content, being classified as coma, unresponsive wakefulness syndrome/vegetative state, minimally conscious confusional state. Patients with willful modulation activity detectable functional MRI or EEG but not behavioral examination a state known covert cognitive motor dissociation. This may every 4th 5th patient without evidence verbal command following has been identified an independent predictor recovery. Underlying mechanisms uncertain intact thalamocortical projections maybe essential. Insights into underlying major importance provide framework to conceptualize treatment approaches, including medical, mechanical, electoral stimulation. Conclusions beginning gain insights DoC, identifying novel advanced prognostication tools improve predictions, starting targeted support patients. It essential determine how advancements implemented benefit across range settings global societal systems. The Curing Coma Campaign highlighted gaps knowledge provides roadmap advance field coma science goal DoC.

Язык: Английский

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Dexmedetomidine Improves Anxiety-like Behaviors in Sleep-Deprived Mice by Inhibiting the p38/MSK1/NFκB Pathway and Reducing Inflammation and Oxidative Stress

Brain Sciences, Год журнала: 2023, Номер 13(7), С. 1058 - 1058

Опубликована: Июль 11, 2023

(1) Background: Sleep deprivation (SD) triggers a range of neuroinflammatory responses. Dexmedetomidine can improve sleep deprivation-induced anxiety by reducing response but the mechanism is unclear; (2) Methods: The model was established using an interference rod device. An open field test and elevated plus maze were used to detect emotional behavior mice. Mouse cortical tissues subjected RNA sequence (RNA-seq) analysis. Western blotting immunofluorescence expression p38/p-p38, MSK1/p-MSK1, NFκBp65/p- NFκBp65. Inflammatory cytokines detected enzyme-linked immunosorbent assay (ELISA); (3) Results: SD triggered anxiety-like behaviors in mice closely associated with inflammatory responses MAPK pathway (as demonstrated transcriptome analysis). led increased levels p-p38, p-MSK1, p-NFκB. P38 inhibitor SB203580 confirm important role p38/MSK1/NFκB SD-induced neuroinflammation. (Dex) effectively improves sleep-deprived attenuating oxidative stress cerebral cortex, mainly inhibiting activation pathway; (4) Conclusions: Dex inhibits pathway, thus cortex

Язык: Английский

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

Опубликована: Янв. 10, 2024

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

Язык: Английский

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Alpha anteriorization and theta posteriorization during deep sleep

Journal of Neuroscience Research, Год журнала: 2024, Номер 102(4)

Опубликована: Апрель 1, 2024

Abstract Brain states (wake, sleep, general anesthesia, etc.) are profoundly associated with the spatiotemporal dynamics of brain oscillations. Previous studies showed that EEG alpha power shifted from occipital cortex to frontal (alpha anteriorization) after being induced into a state anesthesia via propofol. The sleep research literature suggests slow waves and spindles generated locally propagated gradually different regions. Since conceptualized under same framework consciousness, present study examines whether anteriorization similarly occurs during how in other frequency bands changes stages. results analysis three polysomnography datasets 234 participants show consistent stages N 2 3, beta stage REM , theta posteriorization 3. Although it is known neural circuits responsible for not exactly findings this suggest that, at macro level, oscillations organized similar cortical areas. spatial shifts may offer meaningful neurophysiological markers level consciousness.

Язык: Английский

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