Biology subjects

Mashour, G. A.

Publications and source records attributed to Mashour, G. A..

At least 19 recordsLinked to original sources

bioRxiv2026

Reorganization of Human Brain Waves Across Diverse States of Consciousness

Brain waves are ubiquitous phenomena of human brain activity. As they propagate, they coordinate neural communication, shaping conscious perception. Understanding how brain waves unfold across space and time is thus critical for uncovering the neural mechanisms that support and suppress consciousness. Here, we analyzed data from the Human Connectome Project alongside multiple independent human datasets of various states of consciousness collected during non-rapid eye movement sleep, propofol anesthesia, and psychedelic states produced by lysergic acid diethylamide, N,N-dimethyltryptamine, psilocybin, nitrous oxide, and ketamine. We then applied complex principal component analysis to map spatiotemporal propagation patterns of blood oxygen level-dependent activity across the human brain, under these diverse states of consciousness. We identified four dominant motifs of wave propagation: a global synchronized wave supporting unimodal-transmodal propagation, an anti-correlated unimodal-transmodal wave, an anti-correlated task-positive/task-negative wave, and an anti-correlated visual-somatomotor wave. Among them, the global wave exhibited the most pronounced state-dependent reconfiguration: in diminished states (sleep and anesthesia), the time needed for the wave to propagate across brain regions consistently increased and the distribution of regional contributions to the waves power became more spatially concentrated and heterogeneous across individuals, indicating slower, more fragmented, and less stereotyped dynamics. In contrast, propagation duration decreased under psychedelic states, reflecting accelerated global wave dynamics alongside a trend towards more spatially distributed and uniform regional contributions, consistent with a more integrated global wave propagation pattern. Beyond this global mode, diminished states slowed propagation primarily along the unimodal-transmodal axis, whereas psychedelic states selectively accelerated propagation along the task-positive/task-negative axis. Together, our findings reveal that diminished (sleep and anesthesia) and psychedelic states alter the spatiotemporal structure of wave propagation across the brain in opposite and distinct ways, providing a unifying account of how macroscale brain dynamics are dynamically reshaped under pharmacological and endogenous perturbations of consciousness.

neuroscience↗

bioRxiv2026

Opposing Network Patterns of Integration-Segregation in Psychedelic and Sedated States of Consciousness

Understanding the relationship of conscious states to large-scale brain dynamics remains a central challenge in neuroscience. Here, diverse pharmacological and physiological perturbations--including psychedelic states, sleep, and propofol sedation--were used to examine integration-segregation organization of brain networks across altered states of consciousness in humans using functional MRI. Across analyses, psychedelic and sedative states exhibited a robust "mirror-image" pattern of integration and segregation. Psychedelics were characterized by increased large-scale integration and reduced segregation of brain network interactions, whereas sleep and propofol sedation showed the opposite configuration. These opposing integration-segregation patterns were consistently indexed by complementary measures of functional connectivity, network topology, and interaction complexity, capturing non-redundant dimensions of large-scale brain organization. Importantly, this mirror-image organization generalized across multiple spatial levels and reliably differentiated conscious states in an unbiased, data-driven manner. Together, these findings demonstrate that psychedelic and sedated states are characterized by systematic and opposing shifts in large-scale integration and segregation, with implications for mechanisms of consciousness.

neuroscience↗

bioRxiv2025

A Mesoscale Framework for Psychedelic Drug Action in the Human Brain

The mechanism of psychedelic drug action is a dynamic area of neuroscience, with two major lines of investigation: (1) laboratory studies at the molecular and cellular level, and (2) human neuroimaging studies of functional brain networks. Despite considerable progress, there remains insufficient understanding of the link between molecular/cellular substrates of psychedelics and the whole-brain network effects that result. Here we report a study of psychedelic action that focuses on the intermediate spatial scale of local brain regions (<1cm3). We analyzed the effects of classical psychedelics (dimethyltryptamine [DMT], lysergic acid diethylamide [LSD], psilocybin) and non-classical psychedelics (nitrous oxide, ketamine) in humans using functional magnetic resonance imaging. We found that all five drugs reduced regional homogeneity, that is, they disrupted local synchrony, in small-scale brain regions; this disruption occurred extensively in cortical regions and sparsely in subcortical regions. Dynamic analysis of both regional homogeneity and global functional connectivity showed an inverse pattern, with large-scale functional connectivity being enhanced as local synchrony declined. We then conducted dominance analysis to assess the contribution of various neurotransmitter receptors to changes in regional homogeneity. DMT, LSD, and psilocybin showed the 5-HT receptors as the most dominant association; by contrast, regional homogeneity changes attributable to both nitrous oxide and ketamine were most strongly associated with the NMDA receptor. Both neuronal (including interneurons) and non-neuronal cell types were linked to psychedelic-induced changes in synchrony at the level of local brain regions. These data, across five drugs from two drug classes, provide evidence that a diverse set of molecular and cellular events lead to a common outcome of disrupted synchrony in local brain regions, which in turn mediate drug-specific changes in global functional connectivity.

neuroscience↗

bioRxiv2025

Sub-second Fluctuation between Top-Down and Bottom-Up Modes Distinguishes Diverse Human Brain States

Information continuously flows between regions of the human brain, exhibiting distinct patterns that dynamically shift across states of consciousness, cognitive modes, and neuropsychiatric conditions. In this study, we introduce Relative Phase Analysis (RPA), a method that leverages phase-lead/lag relationships to reveal the real-time dynamics of dominant directional patterns and their rapid transitions. We demonstrate that the human brain switches on a sub-second timescale between a top-down mode-where anterior regions drive posterior activity-and a bottom-up mode, characterized by reverse directionality. These dynamics are most pronounced during full consciousness and gradually become less distinct as awareness diminishes. Furthermore, we find from simultaneous EEG-fMRI recordings that the top-down mode is expressed when higher-order cognitive networks are more active while the bottom-up mode is expressed when sensory systems are more active. Moreover, comparisons of an attention deficit hyperactivity disorder (ADHD) inattentive cohort with typically developing individuals reveal distinct imbalances in these transition dynamics, highlighting the potential of RPA as a diagnostic biomarker. Complementing our empirical findings, a coupled-oscillator model of the structural brain network recapitulates these emergent patterns, suggesting that such directional modes and transitions may arise naturally from inter-regional neural interactions. Altogether, this study provides a framework for understanding whole-brain dynamics in real-time and identifies sub-second fluctuations in top-down versus bottom-up directionality as a fundamental mechanism underlying human information processing.

neuroscience↗

bioRxiv2025

Psychedelic-mediated Reversal of General Anesthesia and Restoration of Brain Dynamics in Rat

Serotonergic psychedelics enhance neurophysiological complexity and the repertoire of brain states, whereas general anesthetics produce opposite effects. Serotonergic psychedelics are also known to increase wakefulness and reduce sleep time in rodents. Therefore, we hypothesized that 2,5-dimethoxy-4-iodopamphetamine (DOI), a serotonergic psychedelic, will reverse general anesthesia and restore neurophysiological conditions associated with normal wakefulness. We demonstrate that intravenous administration of DOI in rats under general anesthesia induced wakefulness despite ongoing delivery of the anesthetics, propofol or isoflurane. Behavioral arousal was accompanied by recovery of directional and non-directional high gamma (125-165Hz) functional connectivity and restoration of functional brain network structure. These behavioral and neurophysiological effects were blocked by a 5-HT2A antagonist, volinanserin. Intravenous administration of a non-psychedelic 5-HT2A agonist, lisuride, failed to restore wakefulness or brain dynamics in anesthetized rats. To our knowledge, these results provide the first evidence of psychedelic-mediated reversal of general anesthesia and concurrent restoration of brain dynamics associated with normal wakefulness.

neuroscience↗

bioRxiv2024

Proximity to Explosive Synchronization Determines Network Collapse and Recovery Trajectories in Neural and Economic Crises

When complex systems move away from criticality--a balance between order and chaos--they are no longer optimized. Furthermore, when criticality is lost too quickly, or recovery is delayed, system damage can result. However, the mechanism for these abnormally fast or slow critical transitions remains unknown. Here, we show that the proximity of a complex network to explosive synchronization (ES), a first-order phase transition, determines the trajectories of criticality loss and recovery after perturbations. Our computational models revealed characteristic dynamics based on network proximity to ES, enabling us to infer network phase transition types from empirical data and predict criticality transition patterns. We validated our predictions using empirical data from the human brain under anesthesia and the stock market during an economic crisis, demonstrating that early and prolonged recoveries can be systematically predicted. This study has implications for designing resilient networks that withstand perturbations and recover quickly.

systems biology↗

bioRxiv2024

Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

neuroscience↗

bioRxiv2024

Thalamic Roles in Conscious Perception Revealed by Low-Intensity Focused Ultrasound Neuromodulation

The neural basis of consciousness remains incompletely understood. While cortical mechanisms of conscious perception have been extensively investigated in humans, the role of subcortical structures, including the thalamus, remains less explored. Here, we elucidate the causal contributions of different thalamic regions to conscious perception using transcranial low-intensity focused ultrasound (LIFU) neuromodulation. We hypothesize that modulating distinct thalamic regions alters perceptual outcomes derived from Signal Detection Theory. We apply LIFU to healthy human anterior (transmodal-dominant) and posterior (unimodal-dominant) thalamic regions, further subdivided into ventral and dorsal regions, during a near-threshold visual perception task. We show that high duty cycle modulation of the ventral anterior (VA) part of thalamus enhances object recognition sensitivity. Sensitivity enhancement magnitude correlates with the core-matrix cell compositions of the stimulated thalamic region. Connectivity analysis of a large-scale functional magnetic resonance imaging dataset confirms strong transmodal connectivity of VA thalamus with frontoparietal and default-mode networks. We also demonstrate target-invariant effects of high duty cycle LIFU disrupting object categorization accuracy. These findings provide causal insight into the cytoarchitectural and functional organization of the thalamus that shapes human visual experience, especially the role of matrix cell-rich, transmodal-dominant VA thalamus.

neuroscience↗

bioRxiv2024

Regulation of REM Sleep Onset and Homeostasis by Preoptic Glutamatergic Neurons

The preoptic area of the hypothalamus is key for the control of sleep onset and sleep homeostasis. Although traditionally considered exclusively somnogenic, recent studies identified a group of preoptic glutamatergic neurons that promote wakefulness. Specifically, our previous investigations demonstrated that chemogenetic stimulation of glutamatergic neurons within the medial-lateral preoptic area (MLPO_VGLUT2) promotes wakefulness, fragments non-rapid eye movement sleep (NREMs), and suppresses REM sleep (REMs). This evidence is further supported by recent work showing that preoptic glutamatergic neurons are activated during microarousals that fragment sleep in response to stress, and optogenetic stimulation of these neurons promotes microarousals and wakefulness. Thus, while the wake-promoting function of MLPO_VGLUT2 is clear, their role in sleep homeostasis has not been assessed. We tested the hypothesis that MLPO_VGLUT2 are wake-active, and their activation will increase wakefulness and disrupt sleep homeostasis via projections to arousal-promoting systems. Using fiber photometry, we found that MLPO_VGLUT2 were highly active during REMs, wakefulness and brief arousals, and remained minimally active during NREMs. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REMs onset and suppressed the REMs homeostatic response after total sleep deprivation. Chemogenetic inhibition of MLPO_VGLUT2 increased REMs time (during the light phase only) but did not influence REMs and NREMs homeostasis. Anterograde projection mapping revealed that MLPO_VGLUT2 innervate central regions that promote wakefulness and inhibit REMs. We conclude that MLPO_VGLUT2 powerfully suppress REMs and that exogenous --and possibly pathologic-- activation of these neurons disrupts REMs recovery, presumably by directly or indirectly activating REMs-inhibitory mechanisms. SIGNIFICANCE STATEMENTThe preoptic area of the hypothalamus has been extensively studied and its role in sleep regulation is well-established. Importantly, recent work identified a group of preoptic glutamatergic neurons (MLPO_VGLUT2) that are wake-active and promote wakefulness. However, whether these neurons influence sleep homeostasis remains unknown. We demonstrate that MLPO_VGLUT2 are maximally active during REM sleep (REMs), wakefulness and brief arousals from sleep, and innervate wake-promoting and REMs-inhibitory regions. MLPO_VGLUT2 stimulation inhibits REMs and REMs rebound after sleep deprivation, whereas their inactivation increases REMs but does not alter REMs homeostatic response. We thus identified a preoptic mechanism that powerfully suppresses REMs, which we propose may engage during normal sleep-to-wake transitions to block REMs intrusions into subsequent wakefulness.

neuroscience↗

bioRxiv2024

Neurochemical and Neurophysiological Effects of Intravenous Administration of N,N-dimethyltryptamine in Rats

N,N-dimethyltryptamine (DMT) is a serotonergic psychedelic that is being investigated clinically for the treatment of psychiatric disorders. Although the neurophysiological effects of DMT in humans are well-characterized, similar studies in animal models as well as data on the neurochemical effects of DMT are generally lacking, which are critical for mechanistic understanding. In the current study, we combined behavioral analysis, high-density (32-channel) electroencephalography, and ultra-high-performance liquid chromatography-tandem mass spectrometry to simultaneously quantify changes in behavior, cortical neural dynamics, and levels of 17 neurochemicals in medial prefrontal and somatosensory cortices before, during, and after intravenous administration of three different doses of DMT (0.75 mg/kg, 3.75 mg/kg, 7.5 mg/kg) in male and female adult rats. All three doses of DMT produced head twitch response with most twitches observed after the low dose. DMT caused dose-dependent increases in serotonin and dopamine levels in both cortical sites along with a reduction in EEG spectral power in theta (4-10 Hz) and low gamma (25-55 Hz), and increase in power in delta (1-4 Hz), medium gamma (65-115 ), and high gamma (125-155 Hz) bands. Functional connectivity decreased in the delta band and increased across the gamma bands. In addition, we provide the first measurements of endogenous DMT in these cortical sites at levels comparable to serotonin and dopamine, which together with a previous study in occipital cortex, suggests a physiological role for endogenous DMT. This study represents one of the most comprehensive characterizations of psychedelic drug action in rats and the first to be conducted with DMT. Significance StatementN,N-dimethyltryptamine (DMT) is a serotonergic psychedelic with potential as a tool for probing the neurobiology of consciousness and as a therapeutic agent for psychiatric disorders. However, the neurochemical and neurophysiological effects of DMT in rat, a preferred animal model for mechanistic studies, are unclear. We demonstrate that intravenous DMT caused a dose-dependent increase in serotonin and dopamine in medial prefrontal and somatosensory cortices, and simultaneously increased gamma functional connectivity. Similar effects have been shown for other serotonergic and atypical psychedelics, suggesting a shared mechanism of drug action. Additionally, we report DMT during normal wakefulness in two spatially and functionally distinct cortical sites -- prefrontal, somatosensory -- at levels comparable to those of serotonin and dopamine, supporting a physiological role for endogenous DMT.

neuroscience↗

bioRxiv2024

Measuring the dynamic balance of integration and segregation underlying consciousness, anesthesia, and sleep

Consciousness requires a dynamic balance of integration and segregation in functional brain networks. An optimal integration-segregation balance depends on two key aspects of functional connectivity: global efficiency (i.e., integration) and clustering (i.e., segregation). We developed a new fMRI-based measure, termed the integration-segregation difference (ISD), which captures both aspects. We used this metric to quantify changes in brain state from conscious wakefulness to loss of responsiveness induced by the anesthetic propofol. The observed changes in ISD suggest a profound shift to segregation in both whole brain and all brain subnetworks during anesthesia. Moreover, brain networks displayed similar sequences of disintegration and subsequent reintegration during, respectively, loss and return of responsiveness. Random forest machine learning models, trained with the integration and segregation of brain networks, identified the awake vs. unresponsive states and their transitions with accuracy up to 93%. We found that metastability (i.e., the dynamic recurrence of non-equilibrium transient states) is more effectively explained by integration, while complexity (i.e., diversity and intricacy of neural activity) is more closely linked with segregation. The analysis of a sleep dataset revealed similar findings. Our results demonstrate that the integration-segregation balance is a useful index that can differentiate among various conscious and unconscious states.

neuroscience↗

bioRxiv2024

Propofol Disrupts the Functional Core-Matrix Architecture of the Thalamus in Humans

Research into the role of thalamocortical circuits in anesthesia-induced unconsciousness is difficult due to anatomical and functional complexity. Prior neuroimaging studies have examined either the thalamus as a whole or focused on specific subregions, overlooking the distinct neuronal subtypes like core and matrix cells. We conducted a study of heathy volunteers and functional magnetic resonance imaging during conscious baseline, deep sedation, and recovery. We advanced the functional gradient mapping technique to delineate the functional geometry of thalamocortical circuits, within a framework of the unimodal-transmodal functional axis of the cortex. We observed a significant shift in this geometry during unconsciousness, marked by the dominance of unimodal over transmodal geometry. This alteration was closely linked to the spatial variations in the density of matrix cells within the thalamus. This research bridges cellular and systems-level understanding, highlighting the crucial role of thalamic core-matrix functional architecture in understanding the neural mechanisms of states of consciousness.

neuroscience↗

bioRxiv2023

Cellular rules underlying psychedelic control of prefrontal pyramidal neurons

Classical psychedelic drugs are thought to increase excitability of pyramidal cells in prefrontal cortex via activation of serotonin 2A receptors (5-HT2ARs). Here, we instead find that multiple classes of psychedelics dose-dependently suppress intrinsic excitability of pyramidal neurons, and that extracellular delivery of psychedelics decreases excitability significantly more than intracellular delivery. A previously unknown mechanism underlies this psychedelic drug action: enhancement of ubiquitously expressed potassium "M-current" channels that is independent of 5-HT2R activation. Using machine-learning-based data assimilation models, we show that M-current activation interacts with previously described mechanisms to dramatically reduce intrinsic excitability and shorten working memory timespan. Thus, psychedelic drugs suppress intrinsic excitability by modulating ion channels that are expressed throughout the brain, potentially triggering homeostatic adjustments that can contribute to widespread therapeutic benefits.

neuroscience↗

bioRxiv2023

Intravenous psilocybin administration attenuates mechanical hypersensitivity in a rat model of chronic pain

There is a renewed interest in the therapeutic potential of psychedelics, including psilocybin, in treating mental health disorders. However, there are no data on the efficacy of psilocybin in alleviating chronic pain. In this study, we investigated the effect of psilocybin on mechanical hypersensitivity and thermal hyperalgesia in a rat model of formalin-induced chronic pain. Adult male and female rats were surgically implanted with a jugular vein catheter for psilocybin or saline administration. After two weeks of post-surgical recovery and conditioning, baseline responses to mechanical (von Frey assay) and thermal (hot plate assay) stimuli were measured. Twenty-four hours after baseline measurements, rats received a subcutaneous injection of formalin (5%, 50{micro}L) into one of the hind paws and 2h later, responses to the mechanical and thermal stimuli were measured. Twenty-four hours after formalin injection, rats received an intravenous bolus of 1 mg/kg psilocybin (n=14) or 10 mg/kg psilocybin (n=12) or saline (n=13), and approximately 3h later, responses to the mechanical and thermal stimuli were measured. Rats were tested every other day during week 1, and then weekly for the next 3 weeks. Formalin injection induced thermal hyperalgesia and bilateral mechanical hypersensitivity in the hind paws of all rats. Intravenous psilocybin produced significant attenuation (p<0.05) of the formalin-induced bilateral mechanical hypersensitivity for 28 days but had limited effect (p<0.05 only on days 1, 3, 5, and 21) on thermal hyperalgesia. These data demonstrate that a single intravenous bolus of psilocybin can attenuate indices of chronic pain in a rat model.

neuroscience↗

bioRxiv2023

Psychedelic Concentrations of Nitrous Oxide Reduce Functional Differentiation in Frontoparietal and Somatomotor Cortical Networks

AO_SCPLOWBSTRACTC_SCPLOWDespite the longstanding use of nitrous oxide and descriptions of its psychological effects more than a century ago, there is a paucity of neurobiological investigation of associated psychedelic experiences. Identifying the impact of nitrous oxide on functional brain networks would advance understanding and contribute to the growing body of research in psychedelic neuroscience. Based on human resting-state fMRI data acquired before and during the administration of 35% nitrous oxide, we measured the brains functional geometry (through analysis of cortical gradients) and temporal dynamics (through analysis of co-activation patterns). Both analyses show that nitrous oxide reduces functional differentiation in frontoparietal and somatomotor networks. Importantly, the subjective psychedelic experience induced by nitrous oxide is inversely correlated with the degree of functional differentiation. Thus, like classical psychedelics acting on 5-HT2 receptors, nitrous oxide flattens the functional geometry of the cortex and disrupts temporal dynamics in association with psychoactive effects.

neuroscience↗

bioRxiv2022

Canonical and Non-Canonical Psychedelic Drugs Induce Common Network Changes in Human Cortex

AO_SCPLOWBSTRACTC_SCPLOWThe neurobiology of the psychedelic experience is not fully elucidated. Identifying common brain network changes induced by both canonical (i.e., acting at the 5-HT2 receptor) and non-canonical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all drugs tested increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical "hot zone," posited to mediate the content of consciousness. Thus, both canonical and non-canonical psychedelics modulate networks within an area of known relevance for conscious experience, identifying a biologically plausible candidate for their subjective effects.

neuroscience↗

bioRxiv2020

Criticality Creates a Functional Platform for Network Transitions between Internal and External Processing Modes in the Human Brain

Continuous switching between internal and external modes in the brain is a key process of constructing inner models of the outside world. However, how the brain continuously switches between two modes remains elusive. Here, we propose that a large synchronization fluctuation of the brain network emerging only near criticality (i.e., a balanced state between order and disorder) spontaneously creates temporal windows with distinct preferences for integrating internal information of the network and external stimuli. Using a computational model and empirical data analysis during alterations of consciousness in human, we present that synchronized and incoherent networks respectively bias toward internal and external information with specific network configurations. The network preferences are the most prominent in conscious states; however, they disrupt in altered states of consciousness. We suggest that criticality produces a functional platform of the brains capability for continuous switching between two modes, which is crucial for the emergence of consciousness.

neuroscience↗

bioRxiv2020

Glutamatergic neurons in the preoptic hypothalamus promote wakefulness, destabilize NREM sleep, suppress REM sleep, and regulate cortical dynamics

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. Activation of preoptic glutamatergic neurons also causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons may initiate -but not maintain- arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the conclusion that the preoptic area causally contributes to the regulation of both sleep and wakefulness.

neuroscience↗