Biology subjects

Vanini, G.

Publications and source records attributed to Vanini, G..

9 recordsLinked to original sources

bioRxiv2025

Intravenous Administration of Serotonergic Psychedelics Produce Short-lasting Changes in Sleep-Wake Behavior and High Gamma Functional Connectivity in Rats

Background and PurposeGiven the increase in recreational psychedelic use and ongoing efforts to explore psychedelics as therapeutic agents for mental health disorders, there is an urgent need to understand the effect of psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT) on sleep-wake states, which share a bidirectional relationship with mental health. Here, we investigated the effects of intravenous psilocybin and DMT on sleep-wake states and EEG spectral power and functional connectivity in rats. Experimental ApproachSprague Dawley rats (n=25, 13 male) were surgically instrumented to record high-density EEG (27 electrodes) and EMG during 12-h light and 12-h dark cycle after intravenous psilocybin (2.5 mg/kg, 10 mg/kg), DMT (3.75 mg/kg, 7.5 mg/kg) or 0.9% saline. The EEG/EMG data were scored in 4-second epochs into wake, slow-wave sleep (SWS), and rapid eye movement (REM) sleep. EEG spectral power and corticocortical coherence, a surrogate for functional connectivity, were computed in 12-second epochs. Key ResultsPsilocybin and DMT delayed the onset of SWS and REM sleep, and caused a short-lasting increase in wakefulness and decrease in SWS. Psilocybin also produced a 1) decrease in REM sleep, 2) decrease in theta power and coherence and increase in high gamma power and coherence during wake and SWS, and 3) increase in high gamma coherence during REM sleep. DMT increased gamma coherence only during wakefulness. Conclusions and ImplicationsSerotonergic psychedelics have minimal effects on sleep-wake states. The enhanced high gamma functional connectivity suggests that the psychedelic-induced changes in EEG/neural dynamics can occur independent of the arousal states.

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

Psilocybin induces dose-dependent changes in functional network organization in rat cortex

Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p[≤]0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p[≤]0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.

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↗

bioRxiv2021

Urethane Anesthesia Exhibits Neurophysiological Correlates of Unconsciousness and is Distinct from Sleep

Urethane is a general anesthetic widely used in animal research. It is unique among anesthetics because urethane anesthesia alternates between macroscopically distinct electrographic states: a slow-wave state that resembles NREM sleep (NREMure), and an activated state with features of both REM sleep and wakefulness (REMure). However, the relationship between urethane anesthesia and physiological sleep is still unclear. In this study, electroencephalography (EEG) and electromyography were recorded in chronically prepared rats during natural sleep-wake states and during urethane anesthesia. We subsequently analyzed the EEG signatures associated with the loss of consciousness and found that, in comparison to natural sleep-wake states, the power, coherence, directed connectivity and complexity of brain oscillations are distinct during urethane. We also demonstrate that both urethane states have clear EEG signatures of general anesthesia. Thus, despite superficial similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anesthesia differ from physiological sleep states.

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↗

bioRxiv2020

Power and coherence in the EEG of the rat: impact of behavioral states, cortical area, lateralization and light/dark phases

The sleep-wake cycle is constituted by three behavioral states: wakefulness (W), non-REM (NREM) and REM sleep. These states are associated with drastic changes in cognitive capacities, mostly determined by the function of the thalamo-cortical system. Thalamo-cortical activity can be examined by means of the intra-cranial electroencephalogram (iEEG). With the purpose to study in depth the basal activity of the iEEG in adult rats, we analyzed the spectral power and coherence of the iEEG during W and sleep in the paleocortex (olfactory bulb), as well as in motor, somatosensory and visual neocortical areas. We also analyzed the laterality (right Vs. left hemispheres) of the signals, as well as the iEEG in function of the light and dark phases. We found that the iEEG power and coherence of the whole spectrum were largely affected by behavioral states and were highly dependent on the cortical areas recorded. We also determined that there are night/day differences in power and coherence during sleep, but not in W. Finally, while we did not find right/left differences in power either in W or sleep, we observed that during REM sleep intra-hemispheric coherence differs between both hemispheres. We conclude that the iEEG dynamics is highly dependent on the cortical area and behavioral states. We also determine that there are light/dark phases disparities in the iEEG that emerge during sleep, and that intra-hemispheric connectivity differs between both hemispheres only during REM sleep.

neuroscience↗

bioRxiv2020

Recovery of Consciousness and Cognition after General Anesthesia in Humans

Understanding how consciousness and cognitive function return after a major perturbation is important clinically and neurobiologically. To address this question, we conducted a three-center study of 30 healthy humans receiving general anesthesia at clinically relevant doses for three hours. We administered a pre- and post-anesthetic battery of neurocognitive tests, recorded continuous electroencephalography to assess cortical dynamics, and monitored sleep-wake activity before and following anesthetic exposure. We hypothesized that cognitive reconstitution would be a process that evolved over time in the following sequence: attention, complex scanning and tracking, working memory, and executive function. Contrary to our hypothesis, executive function returned first and electroencephalographic analyses revealed that frontal cortical dynamics recovered faster than posterior cortical dynamics. Furthermore, actigraphy indicated normal sleep-wake patterns in the post-anesthetic period. These recovery patterns of higher cognitive function and arousal states suggest that the healthy human brain is resilient to the effects of deep general anesthesia.

neuroscience↗

bioRxiv2020

Brain network motifs are markers of loss and recovery of consciousness

Motifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-hour anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8-13 Hz) band, five-minute epochs of EEG were extracted for: baseline; induction; unconscious; 30-, 10- and 5-minutes pre-recovery of responsiveness; 30- and 180-minutes post-recovery of responsiveness. We constructed a functional brain network using the weighted and directed phase lag index, on which we calculated the frequency and topology of 3-node motifs. Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p<0.05). The topology of motifs 1 and 5 changed significantly between responsive and unresponsive epochs (p<0.01). Motif 1 was constituted by long-range chain-like connections, while motif 5 was constituted by short-range, loop-like connections. Our results suggest that anesthetic-induced unconsciousness is associated with a topological re-organization of network motifs. As motif topological re-organization may precede (motif 5) or accompany (motif 1) the return of responsiveness, motifs could contribute to the understanding of the neural correlates of consciousness.

neuroscience↗