Potential Rhythms of the Cerebral Cortex During Sleep

Loomis, A. L.; Harvey, E. Newton; Hobart, G.

doi:10.1126/science.81.2111.597

Cited by 339 publications

(132 citation statements)

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“…Eighty years after the first description by the pioneers of EEG recordings [1,2], sleep spindles have developed into a topical subject lying at the intersection of major areas of research in the neurosciences. The cellular and circuit bases of these unique EEG rhythms have been studied for decades in vitro, in vivo and in computo [3,4], whereas, more recently, the search for their neurobiological functions has gained considerable attention.…”

Section: Sleep Spindles: From Their First Identification To Their Molmentioning

confidence: 99%

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Astori

Wimmer²,

Lüthi³

2013

Trends in Neurosciences

135

113

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Abstract:Sleep spindles are distinctive electroencephalographic (EEG) oscillations emerging during non-rapid-eye-movement sleep (NREMS) that have been implicated in multiple brain functions, including sleep quality, sensory gating, learning and memory. Despite considerable knowledge about the mechanisms underlying these neuronal rhythms, their function remains poorly understood and current views are largely based on correlational evidence. Here, we review recent studies in humans and rodents that have begun to broaden our understanding of the role of spindles in the normal and disordered brain. We show that newly identified molecular substrates of spindle oscillations, in combination with evolving technological progress, offer novel targets and tools to selectively manipulate spindles and dissect their role in sleep-dependent processes. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationAstori et al. Highlights Newly recognized ion channel subtypes generating spindle rhythms are described. The contribution of spindles to arousal threshold and sleep quality is discussed. The proposed role of spindles in memory consolidation is examined. A function of thalamic spindles in neural development is suggested. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 4 Previous excellent reviews have thoroughly described cellular and network bases of spindle generation [3,6,7]. Here, we first review recent work on genetic models that has expanded the mechanistic understanding of this EEG rhythm through the modification of novel molecular substrates. We then discuss the current views about the functional aspects of spindles in brain physiology and pathology, as obtained from studies in naturally sleeping animals and humans. We highlight studies indicating that spindles are accessible for selective interventions, and that, with emerging technologies, will open avenues to decipher spindle function. Novel molecular aspects of spindle generationSleep spindles emerge from a limited set of cellular participants: the resonating core of these waxing-and-waning oscillations resides in the nRt-TC loop, which sustains repetitive burst discharges of its cellular components under the control of cortical inputs (Figure 1 Another important factor in the generation and maintenance of reticular intrinsic oscillations is the aforementioned SK2 or Kcnn2 channel. The vigorous Ca 2+ influx in nRt dendrites originating from Ca V 3.3 channels gates SK2 channels, thereby creating a burstafterhyperpolarization (bAHP) [12,19]. As T channels recover partially from inactivation duri...

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Section: Sleep Spindles: From Their First Identification To Their Molmentioning

confidence: 99%

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Astori

Wimmer²,

Lüthi³

2013

Trends in Neurosciences

135

113

View full text Add to dashboard Cite

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“…T he electrical activity of the cerebral cortex has been used to distinguish sleep vs. wakefulness since the earliest EEG studies of sleep (1). Several neural circuits have been implicated in the synchronization and desynchronization of cortical activity that distinguish non-rapid eye movement sleep (NREM) from wakefulness and rapid eye movement sleep (REM).…”

mentioning

confidence: 99%

A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

Morairty

Dittrich

Pasumarthi

et al. 2013

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

125

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Although the neural circuitry underlying homeostatic sleep regulation is little understood, cortical neurons immunoreactive for neuronal nitric oxide synthase (nNOS) and the neurokinin-1 receptor (NK1) have been proposed to be involved in this physiological process. By systematically manipulating the durations of sleep deprivation and subsequent recovery sleep, we show that activation of cortical nNOS/NK1 neurons is directly related to non-rapid eye movement (NREM) sleep time, NREM bout duration, and EEG δ power during NREM sleep, an index of preexisting homeostatic sleep drive. Conversely, nNOS knockout mice show reduced NREM sleep time, shorter NREM bouts, and decreased power in the low δ range during NREM sleep, despite constitutively elevated sleep drive. Cortical NK1 neurons are still activated in response to sleep deprivation in these mice but, in the absence of nNOS, they are unable to up-regulate NREM δ power appropriately. These findings support the hypothesis that cortical nNOS/NK1 neurons translate homeostatic sleep drive into up-regulation of NREM δ power through an NO-dependent mechanism.T he electrical activity of the cerebral cortex has been used to distinguish sleep vs. wakefulness since the earliest EEG studies of sleep (1). Several neural circuits have been implicated in the synchronization and desynchronization of cortical activity that distinguish non-rapid eye movement sleep (NREM) from wakefulness and rapid eye movement sleep (REM). Input from the basal forebrain (BF), likely from both cholinergic and noncholinergic neurons, is critical for the desynchronized EEG characteristic of wakefulness and REM (2, 3). Synchronization of the EEG during NREM depends on thalamic as well as intrinsic cortical oscillators (4).The firing rate of cortical neurons has generally been reported to be reduced during NREM relative to wakefulness and REM (5, 6). A few studies have reported cortical neurons with the opposite pattern. For example, 4 of 177 neurons in the monkey orbitofrontal cortex increased their firing rates during NREM (7). In the cat parietal cortex, 25% of neurons discharged in phase with NREM slow waves during up states but ceased firing during quiet wakefulness (8).Using Fos immunohistochemistry as a marker of cellular activity, we described a population of cortical GABAergic interneurons that are activated during sleep in three species (9, 10). These neurons express neuronal nitric oxide synthase (nNOS) and thus likely release nitric oxide (NO) as well as GABA (11). The percentage of activated cortical nNOS neurons was proportional to NREM δ energy (NRDE), the product of NREM time and NREM EEG δ power. Because NREM time and δ power increase in response to prolonged wakefulness through a regulated process referred to as sleep homeostasis, NRDE is an electrophysiological marker of homeostatic sleep "drive." Consequently, activation of cortical nNOS neurons during sleep seems to be related to the sleep need that accrues during wakefulness.Cortical nNOS neurons receive cholinergic (12), monoamin...

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“…He reported changes in the pattern of the EEG between periods of mental engagement and resting. The EEG was first monitored during sleep in 1935 (Loomis, Harvey, & Hobart, 1935). The EEG has become the gold standard for classifying and studying the stages of sleep (Rechtschaffen & Kales, 1968).…”

Section: Description Of Eegmentioning

confidence: 99%

Operator Functional State Assessment (L'evaluation de l'aptitude operationnelle de l'operateur humain)

2004

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Potential Rhythms of the Cerebral Cortex During Sleep

Cited by 339 publications

References 1 publication

Manipulating sleep spindles – expanding views on sleep, memory, and disease

Manipulating sleep spindles – expanding views on sleep, memory, and disease

A role for cortical nNOS/NK1 neurons in coupling homeostatic sleep drive to EEG slow wave activity

Operator Functional State Assessment (L'evaluation de l'aptitude operationnelle de l'operateur humain)

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