Staying awake puts pressure on brain arousal systems

Tononi, Giulio; Cirelli, Chiara

doi:10.1172/jci34250

Cited by 13 publications

(9 citation statements)

References 16 publications

(16 reference statements)

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“…This result is also supported by the data of Rao and colleagues (Rao et al 2007), who demonstrated that prolonged wake in mice, induced by gentle handling or modafinil, increases presynaptic glutamatergic input to hypocretin neurons. As reported for other glutamatergic systems in the brain (Tononi & Cirelli 2007), hypocretin neurons may thus increase activity with extended wake, resulting in long term potentiation. In the process, hypocretin neurons, therefore, may be acting as a counter for daily wake until the process becomes somehow unsustainable, then reducing activity and inducing sleep.…”

Section: Discussionsupporting

confidence: 53%

Modafinil and γ-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep

Zeitzer¹,

Buckmaster²,

Landolt³

et al. 2009

Behavioural Pharmacology

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Hypocretin-1 is a hypothalamic neuropeptide that is important in the regulation of wake and the lack of which results in the sleep disorder narcolepsy. Using a monkey that has consolidated wake akin to humans, we examined pharmacological manipulation of sleep and wake and its effects on hypocretin physiology. Monkeys were given the sleep-inducing gamma-hydroxybutyrate (GHB) and the wake-inducing modafinil both in the morning and in the evening. Cerebrospinal fluid (CSF) hypocretin-1 concentrations changed significantly in response to the drugs only when accompanied by a behavioral change (GHB-induced sleep in the morning or modafinil-induced wake in the evening). We also found that there was a large (180-fold) inter-individual variation in GHB pharmacokinetics that explains variability in sleep-induction in response to the drug. Our data indicate that the neurochemical concomitants of sleep and wake are capable of changing the physiological output of hypocretin neurons. Sleep independent of circadian timing is capable of decreasing CSF hypocretin-1 concentrations. Furthermore, hypocretin neurons do not appear to respond to an "effort" to remain awake, but rather keep track of time spent awake as a wake-promoting counterbalance to extended wakefulness.

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Section: Discussionsupporting

confidence: 53%

Modafinil and γ-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep

Zeitzer¹,

Buckmaster²,

Landolt³

et al. 2009

Behavioural Pharmacology

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“…Global synaptic strength in underlying cortical networks may be low in the beginning of the wake phase, i.e., the time the experiments were conducted, in comparison with conditions in the evening when synaptic potentiation has accumulated over the day (32). On this background, the stimulation-induced increase in slow oscillation activity would be expected to be more pronounced after prolonged waking.…”

Section: Discussionmentioning

confidence: 99%

Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding

Kirov

Weiss

Siebner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

190

170

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The application of transcranial slow oscillation stimulation (tSOS; 0.75 Hz) was previously shown to enhance widespread endogenous EEG slow oscillatory activity when applied during a sleep period characterized by emerging endogenous slow oscillatory activity. Processes of memory consolidation typically occurring during this state of sleep were also enhanced. Here, we show that the same tSOS applied in the waking brain also induced an increase in endogenous EEG slow oscillations (0.4 -1.2 Hz), although in a topographically restricted fashion. Applied during wakefulness tSOS, additionally, resulted in a marked and widespread increase in EEG theta (4 -8 Hz) activity. During wake, tSOS did not enhance consolidation of memories when applied after learning, but improved encoding of hippocampus-dependent memories when applied during learning. We conclude that the EEG frequency and related memory processes induced by tSOS critically depend on brain state. In response to tSOS during wakefulness the brain transposes stimulation by responding preferentially with theta oscillations and facilitated encoding.transcranial slow oscillation stimulation ͉ sleep ͉ plasticity ͉ cortex ͉ tDCS (transcranial direct current stimulation)

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“…This positive feedback loop may help to synchronize the firing of the whole orexin neuron population. Furthermore, glutamatergic inputs to orexin neurons are potentiated via a cAMP-dependent mechanism during prolonged waking (1047), which is a mechanism suggested to be important in the maintenance of wakefulness in the face of increased sleep pressure (1299). However, recent optogenetic stimulation experiments found that sleep deprivation blocks the ability of orexin to activate its downstream targets and enhance waking (195).…”

Section: Wakefulnessmentioning

confidence: 99%

Control of Sleep and Wakefulness

Brown

Basheer

Mckenna

et al. 2012

Physiological Reviews

1,168

1,105

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This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

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Staying awake puts pressure on brain arousal systems

Cited by 13 publications

References 16 publications

Modafinil and γ-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep

Modafinil and γ-hydroxybutyrate have sleep state-specific pharmacological actions on hypocretin-1 physiology in a primate model of human sleep

Slow oscillation electrical brain stimulation during waking promotes EEG theta activity and memory encoding

Control of Sleep and Wakefulness

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