Biology subjects

Vyazovskiy, V. V.

Publications and source records attributed to Vyazovskiy, V. V..

26 records · Page 2Linked to original sources

bioRxiv2021

Intraneuronal chloride levels encode tiredness in cortex

Continuous periods of wakefulness are associated with reduced performance levels due to the build-up of sleep pressure in active regions of the brain. These effects manifest as use-dependent changes in cortical network activity and the mechanisms underlying these changes represent targets for overcoming the cognitive effects of tiredness. Here we reveal a central role for intraneuronal chloride levels, which increase in a use-dependent manner during waking, and reduce the strength of local synaptic inhibition in mouse cortex. Activity-dependent increases in chloride account for spatial and temporal features of sleep pressure, they underlie cortical network oscillations in the sleep-deprived state, and targeting chloride regulation in cortex can rescue performance levels when tired. These findings provide a missing link between sleep-wake history, synaptic transmission and cortical dynamics. One-Sentence SummaryThe effects of sleep pressure on cortical function are caused by use-dependent changes in chloride-mediated synaptic inhibition.

neuroscience↗

bioRxiv2021

Psilocin acutely disrupts sleep and affects local but not global sleep homeostasis in laboratory mice

Serotonergic psychedelic drugs, such as psilocin (4-hydroxy-N,N-dimethyltryptamine), profoundly alter the quality of consciousness through mechanisms which are incompletely understood. Growing evidence suggests that a single psychedelic experience can positively impact long-term psychological well-being, with relevance for the treatment of psychiatric disorders, including depression. A prominent factor associated with psychiatric disorders is disturbed sleep, and the sleep-wake cycle is implicated in the regulation of neuronal firing and activity homeostasis. It remains unknown to what extent psychedelic agents directly affect sleep, in terms of both acute arousal and homeostatic sleep regulation. Here, chronic in vivo electrophysiological recordings were obtained in mice to track sleep-wake architecture and cortical activity after psilocin injection. Administration of psilocin led to delayed REM sleep onset and reduced NREM sleep maintenance for up to approximately 3 hours after dosing, and the acute EEG response was associated primarily with an enhanced oscillation around 4 Hz. No long-term changes in sleep-wake quantity were found. When combined with sleep deprivation, psilocin did not alter the dynamics of homeostatic sleep rebound during the subsequent recovery period, as reflected in both sleep amount and EEG slow wave activity. However, psilocin decreased the recovery rate of sleep slow wave activity following sleep deprivation in the local field potentials of electrodes targeting medial prefrontal and surrounding cortex. It is concluded that psilocin affects both global vigilance state control and local sleep homeostasis, an effect which may be relevant for its antidepressant efficacy.

neuroscience↗

bioRxiv2020

Waking experience modulates sleep need in mice

Homeostatic regulation of sleep is reflected in the maintenance of a daily balance between sleep and wake. Although numerous internal and external factors can influence sleep, it is unclear whether and to what extent the process that keeps track of time spent awake is determined by the content of the waking experience. We hypothesised that alterations in environmental conditions may elicit different types of wakefulness, which will in turn influence both the capacity to sustain continuous wakefulness as well the rates of accumulating sleep pressure. To address this, we performed two experiments, where we compared wakefulness dominated by novel object exploration with either (i) the effects of voluntary wheel running (Experiment 1) or (ii) performance in a simple touchscreen task (Experiment 2). We find that voluntary wheel running results in longer wake episodes, as compared with exploratory behaviour; yet it does not lead to higher levels of EEG slow wave activity (SWA) during subsequent sleep. On the other hand, engagement in a touchscreen task, motivated by a food reward, results in lower SWA during subsequent sleep, as compared to exploratory wakefulness, even though the total duration of wakefulness was similar. Overall, our study suggests that sleep-wake behaviour is highly flexible within an individual, and that the homeostatic process that keeps track of time spent awake is sensitive to the nature of the waking experience. We therefore conclude that sleep dynamics are determined, to a large degree, by the interaction between the organism and the environment.

neuroscience↗

bioRxiv2020

The role of the hypothalamus in cortical arousaland sleep homeostasis

Sleep and wakefulness are not simple homogenous all-or-none states, but instead are characterized by rich dynamics of brain activity across many temporal and spatial scales. Rapid global state transitions between waking and sleeping are believed to be controlled by hypothalamic circuits, but the contribution of the hypothalamus to within-state changes of sleep and wake "intensity" remains largely unexplored. Here we show that stimulation of inhibitory neurons in the preoptic hypothalamus does not merely trigger awakening from sleep, but the resulting awake state is also characterized by increased cortical activity. This activation is associated with a faster build-up of sleep pressure, proportional to the arousal level. These findings show that hypothalamic systems thought to exclusively control global state switching, also regulate within-state "intensity", which we propose as a key intrinsic variable in shaping the architecture of sleep/wake states across the 24h day.

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bioRxiv2020

The relationship between fasting-induced torpor,sleep and wakefulness in the laboratory mouse

Torpor is a regulated reversible state of metabolic suppression used by many mammalian species to conserve energy. Although torpor has been studied extensively in terms of general physiology, metabolism and neuroendocrinology, the effects of hypometabolism and associated hypothermia on brain activity and states of vigilance have received little attention. Here we performed continuous monitoring of electroencephalogram (EEG), electromyogram (EMG) and peripheral body temperature in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding. All animals showed prominent bouts of hypothermia that became progressively deeper and longer as fasting progressed. EEG and EMG were markedly affected by hypothermia, although the typical electrophysiological signatures of NREM sleep, REM sleep and wakefulness allowed us to perform vigilance-state classification in all cases. Invariably, hypothermia bouts were initiated from a state indistinguishable from NREM sleep, with EEG power decreasing gradually in parallel with decreasing body temperature. Furthermore, during deep hypothermia REM sleep was largely abolished, but we observed brief and intense bursts of muscle activity, which resembled the regular motor discharges seen during early ontogeny associated with immature sleep patterns. We conclude that torpor and sleep are electrophysiologically on a continuum, and that, in order for torpor to occur, mice need to first transition through euthermic sleep.

neuroscience↗

bioRxiv2020

A role for the cortex in sleep-wake regulation

The cortex and subcortical circuitry are thought to play distinct roles in the generation of sleep oscillations and global control of vigilance states. Here we silenced a subset of cortical layer 5 pyramidal and dentate gyrus granule cells in mice using a cell-specific ablation of the key t-SNARE protein SNAP25. We found a marked increase in wakefulness accompanied by a reduced rebound of EEG slow-wave activity after sleep deprivation. Our data illustrates an important role for the cortex in both global state control and sleep homeostasis.

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bioRxiv2020

Aberrant synaptic release underlies sleep/wake transition deficits in a mouse Vamp2 mutant

Sleep-wake transitions are modulated through extensive subcortical networks although the precise roles of their individual components remain elusive. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterised by a reduced propensity to transition between all sleep states while a profound loss in total REM sleep time was evident. The causative mutation, an Ile102Asn substitution in VAMP2, was associated with substantial synaptic changes while in vitro electrophysiological investigations with fluorescence imaging revealed a diminished probability of vesicular release in mutants. We conclude that the synaptic efficiency of the entire subcortical brain network determines the likelihood that an animal transitions from one vigilance state to the next.

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bioRxiv2019

Cortical neuronal activity determines the dynamics of local sleep homeostasis

The homeostatic regulation of sleep manifests as a relative constancy of its daily amount and intensity. Theoretical descriptions of this phenomenon define "Process S", a variable with dynamics dependent only on sleep-wake history, whose levels are reflected in electroencephalogram (EEG) slow wave activity (0.5 - 4 Hz) during sleep. Here we developed novel mathematical models of Process S in mice, assuming that its dynamics are a function of the deviation of cortical neuronal firing rates from a locally defined set-point, crucially without explicit knowledge of sleep-wake state. Our results suggest that Process S tracks global sleep-wake history through an integration of local cortical neuronal activity levels over time. We posit that, instead of reflecting sleep-wake-dependent changes in specific variables and serving their homeostatic regulation, Process S may be a time-keeping mechanism which enables individuals to obtain a species-specific and ecologically-relevant quantity of sleep, even in the absence of external temporal information.

neuroscience↗