Leak potassium channels regulate sleep duration

Yoshida, Kan; Shi, Shoi; Ukai-Tadenuma, Maki; Fujishima, Hiroshi; Ohno, Rei-ichiro; Ueda, Hiroki R.

doi:10.1073/pnas.1806486115

Cited by 44 publications

(44 citation statements)

References 27 publications

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“…Notably, it is recently shown that the changes in the composition of cortical interstitial Ca 2+ and K + ions influence the sleep-wake cycle (Ding et al, 2016). This study suggests that the intrinsic properties of neural oscillation may depend on the intracellular concentration of Ca 2+ and K + ions, which is in line with the observations that the loss of Ca 2+ and K + channels, such as SK2 (Kcnn2) and SK3 (Kcnn3), Cav3.1 (Cacna1g), Cav3.2 (Cacna1h), and TASK3 (Kcnk9), affected the sleep duration in vivo (Tatsuki et al, 2016;Yoshida et al, 2018).…”

Section: Molecular Mechanisms Of the Bimodality: Up And Down States Osupporting

confidence: 87%

Molecular Mechanisms of REM Sleep

Yamada

Ueda

2020

Front. Neurosci.

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Rapid-eye movement (REM) sleep is a paradoxical sleep state characterized by brain activity similar to wakefulness, rapid-eye-movement, and lack of muscle tone. REM sleep is a fundamental brain function, evolutionary conserved across species, including human, mouse, bird, and even reptiles. The physiological importance of REM sleep is highlighted by severe sleep disorders incurred by a failure in REM sleep regulation. Despite the intense interest in the mechanism of REM sleep regulation, the molecular machinery is largely left to be investigated. In models of REM sleep regulation, acetylcholine has been a pivotal component. However, even newly emerged techniques such as pharmacogenetics and optogenetics have not fully clarified the function of acetylcholine either at the cellular level or neural-circuit level. Recently, we discovered that the G q type muscarinic acetylcholine receptor genes, Chrm1 and Chrm3, are essential for REM sleep. In this review, we develop the perspective of current knowledge on REM sleep from a molecular viewpoint. This should be a starting point to clarify the molecular and cellular machinery underlying REM sleep regulation and will provide insights to explore physiological functions of REM sleep and its pathological roles in REM-sleep-related disorders such as depression, PTSD, and neurodegenerative diseases.

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Section: Molecular Mechanisms Of the Bimodality: Up And Down States Osupporting

confidence: 87%

Molecular Mechanisms of REM Sleep

Yamada

Ueda

2020

Front. Neurosci.

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“…3a). These fluctuations in the cortical response during SWS might be linked to ON/OFF oscillations, which are hypothesized to be caused by shifts in excitability 23,24 , and thus the response amplitude. We therefore separated the evoked responses into ON and OFF according to the LFP preceding the optogenetic stimulation (see Materials and Methods; Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The mechanisms underlying ON/ OFF transitions in SWS are still not well understood. Fluctuations in excitability due to intrinsic mechanisms such as intracellular calcium influx triggering Ca 2+ -dependent K + channels or fluctuations in potassium leak channel availability are postulated 23,24 to underlie the transition to the DOWN state. Alternatively, or in addition, synaptic exhaustion might produce a functional disconnect between cortical neurons and a transition to the DOWN state 48,49 .…”

Section: Discussionmentioning

confidence: 99%

Enhanced cortical responsiveness during natural sleep in freely behaving mice

Matsumoto

Ohyama

Díaz

et al. 2020

Sci Rep

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cortical networks exhibit large shifts in spontaneous dynamics depending on the vigilance state. Waking and rapid eye movement (ReM) sleep are characterized by ongoing irregular activity of cortical neurons while during slow wave sleep (SWS) these neurons show synchronous alterations between silent (off) and active (on) periods. the network dynamics underlying these phenomena are not fully understood. Additional information about the state of cortical networks can be obtained by evaluating evoked cortical responses during the sleep-wake cycle. We measured local field potentials (LFP) and multi-unit activity (MUA) in the cortex in response to repeated brief optogenetic stimulation of thalamocortical afferents. Both LFP and MUA responses were considerably increased in sleep compared to waking, with larger responses during SWS than during REM sleep. The strongly increased cortical response in SWS is discussed within the context of SWS-associated neuro-modulatory tone that may reduce feedforward inhibition. Responses to stimuli were larger during SWS-off periods than during SWS-ON periods. SWS responses showed clear daily fluctuation correlated to light-dark cycle, but no reaction to increased sleep need following sleep deprivation. potential homeostatic synaptic plasticity was either absent or masked by large vigilance-state effects.Behaviorally, sleep is characterized by loss of consciousness, increased arousal threshold, and immobility 1 . Despite decreased communication with the periphery during sleep, cortical neurons remain almost as active as during waking, although the pattern is strikingly different. The activity switches from ongoing irregular action potential firing during waking to synchronized rhythmic oscillations between silent (OFF) and active (ON) periods 2,3 , called slow wave activity in non-rapid eye movement (NREM) sleep or slow wave sleep (SWS), indicating a profound change in the functional cortical architecture. The underlying mechanisms of this switch and the consequences for cortical function and behavior are not fully understood.In addition to observations of spontaneous oscillations, measurements of evoked cortical responses can be used to probe the functional state of the cortical network during waking and sleep 4-11 . Sensory stimuli can reach the cortex during SWS, which allows for studying the effect of wake-sleep transitions on cortical responsiveness 7-10 . Cortical reactivity indeed changes between waking and sleep, but the effect is strongly dependent on the sensory modality and type of stimulus. In the somatosensory cortex, both response depression and enhancement are observed during sleep compared with waking. In human subjects, sensory evoked potentials are smaller during NREM sleep compared with waking 7 . In macaques, responses to tactile stimuli are significantly decreased during SWS compared with waking 8 . Electrical activation of the medial lemniscus results in smaller responses in SWS compared with those in the preceding waking episode 11 . On the other hand, whisker defl...

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“…The sleepless gene antagonizes nAChRs, and lynx1, a mammalian homolog, can partially restore normal sleep to mutants [Wu et al, 2014]. [Yoshida et al, 2018] generated 14 types of leak KC knockout mice, and in all of them sleep duration decreased. Moreover, they implemented a computational model showing that leak KCs can regulate SWA-like EEG along with Ca 2+ channels.…”

Section: Nrem Sleepmentioning

confidence: 99%

A Complete Biological Theory of Sleep

Rappoport¹

2019

Preprint

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Sleep is still considered a mystery, despite intense scientific investigation. Here we present the first complete biological theory of sleep. The role of sleep is to restore the optimal homeostatic state, which is essential for tissue performance and health. Non-rapid eye movement sleep (NREMS) restores cortical and most other brain neurons, via relaxed global activity managed by thalamocortical circuits. The role of REM sleep is to restore acetylcholine (ACh) neurons, which support focused responses and hence cannot participate in global oscillations. Sleep enhances learning and memory via state restoration and ACh-affected paths. NREMS induces a lack of consciousness because global synchronous activity prevents focused responses, which are essential for consciousness. Dreams result from focused neural firing during sharp-wave ripples and REMS, and have a sense of reality because they involve the same neurons representing focused perceptual responses during wake. Anesthetics utilize a variety of mechanisms that prevent focused responses.

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Leak potassium channels regulate sleep duration

Cited by 44 publications

References 27 publications

Molecular Mechanisms of REM Sleep

Molecular Mechanisms of REM Sleep

Enhanced cortical responsiveness during natural sleep in freely behaving mice

A Complete Biological Theory of Sleep

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