Sleep and the single neuron: the role of global slow oscillations in individual cell rest.
TL;DR: This work proposes that sleep's primary function is to allow individual neurons to perform prophylactic cellular maintenance, and suggests that periods of reduced synaptic input ('off periods' or 'down states') are necessary for such maintenance.
Abstract: Sleep is universal in animals, but its specific functions remain elusive. We propose that sleep's primary function is to allow individual neurons to perform prophylactic cellular maintenance. Just as muscle cells must rest after strenuous exercise to prevent long-term damage, brain cells must rest after intense synaptic activity. We suggest that periods of reduced synaptic input ('off periods' or 'down states') are necessary for such maintenance. This in turn requires a state of globally synchronized neuronal activity, reduced sensory input and behavioural immobility - the well-known manifestations of sleep.
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TL;DR: This Perspective considers the rationale and evidence for the synaptic homeostasis hypothesis (SHY), and points to open issues related to sleep and plasticity.
1,565 citations
Cites background from "Sleep and the single neuron: the ro..."
...The available evidence suggests that this may be the case, but only when wake is forced beyond its physiological duration (Braun et al., 1997; Buysse et al., 2004; Shannon et al., 2013; Vyazovskiy et al., 2004)....
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TL;DR: A coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non–rapid eye movement sleep is discovered, demonstrating that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and theseCSF dynamics are interlinked with neural and hemodynamic rhythms.
Abstract: Sleep is essential for both cognition and maintenance of healthy brain function. Slow waves in neural activity contribute to memory consolidation, whereas cerebrospinal fluid (CSF) clears metabolic waste products from the brain. Whether these two processes are related is not known. We used accelerated neuroimaging to measure physiological and neural dynamics in the human brain. We discovered a coherent pattern of oscillating electrophysiological, hemodynamic, and CSF dynamics that appears during non-rapid eye movement sleep. Neural slow waves are followed by hemodynamic oscillations, which in turn are coupled to CSF flow. These results demonstrate that the sleeping brain exhibits waves of CSF flow on a macroscopic scale, and these CSF dynamics are interlinked with neural and hemodynamic rhythms.
478 citations
TL;DR: Much refinement of ideas and innovative experimental approaches are needed to clarify the sleep-connectivity relationship, and the ideas surrounding the broad hypothesis that sleep serves a connectivity/plasticity function are many and attractive.
267 citations
TL;DR: A novel view of sleep in adjusting network excitability is provided, observing that the distribution of pyramidal cell firing rates was wide and strongly skewed toward high firing rates and that the net result of sleep was to homogenize the firing rate distribution.
246 citations
Cites background or methods or result from "Sleep and the single neuron: the ro..."
...A prediction of SHY is that the most active cells and synapses during waking continue to be active during sleep, whereas weak synapses and slow-firing neurons are ‘‘down-selected,’’ that is, eliminated from network activity (Tononi and Cirelli, 2003; Vyazovskiy and Harris, 2013)....
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...In contrast to the hypothesized coupling between downscaling and slow oscillations (Tononi and Cirelli, 2003; Vyazovskiy and Harris, 2013), we found an inverse correlation between various features of slow oscillations and firing rates of fast-firing pyramidal neurons, coupledwith a positive correlationwith slowfiring neurons, resulting in a decreased dispersion of population firing rates (Figure 6)....
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...According to the SHY model, neurons and synapses are overused after extended waking, and nonREM brings about recuperative changes by downscaling the network (Tononi and Cirelli, 2014; Vyazovskiy and Harris, 2013)....
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...…of slow-firing neurons during sleep is in disagreement with a core implication of the SHY model, which implies that sleep should eliminate slow-firing neurons by the repeated silencing of network activity during slow oscillations of nonREM (Tononi and Cirelli, 2014; Vyazovskiy and Harris, 2013)....
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...In the SHY model, the DOWN state of slow oscillation plays a central role: ‘‘periods of reduced synaptic input (‘off periods’ or ‘down states’) are necessary’’ for downscaling synapses and firing rates (Vyazovskiy and Harris, 2013)....
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References
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Book•
01 Jan 1989
TL;DR: Part 1: Normal Sleep and Its Variations; Part 2: Abnormal Sleep.
Abstract: 1. Normal Sleep and Its Variations History Of Sleep Physiology And Medicine Normal Human Sleep: An Overview Normal Ageing Daytime Sleepiness And Alertness Sleep Deprivation Phylogeny Of Sleep Regulation Mammalian Sleep 2. Sleep Mechanisms Brain Electrical Activity And Sensory Processing During Waking And Sleep States Brainstem Mechanisms Generating REM Sleep Basic Mechanisms Of Sleep-Wake States Control Of Motoneurons During Sleep 3. Physiology in Sleep Physiological Regulation in Sleep Cardiovascular Physiology: Central and Autonomic Regulation Cardiovascular Physiology: The Peripheral Circulation Respiratory Physiology: Central Neural Control Respiratory Physiology: Control of Ventilation Respiratory Physiology: Breathing in Normal Subjects Respiratory Physiology: Sleep at High Altitudes Host Defense Endocrine Physiology Gastrointestinal Physiology Temperature Regulation **Sleep-related Penile Erections 4. Chronobiology Introduction: Chronobiology Circadian Rhythms in Mammals: Formal Properties and Environmental Influences Anatomy and Physiology of the Mammalian Circadian System Molecular Genetic Basis for Mammalian Circadian System The Human Circadian Timing System and Sleep-Wake Regulation **Sleep Homeostasis and Models of Sleep Regulation Circadian Rhythms in Fatigue, Alertness and Performance Melatonin in the Regulations of Sleep & Circadian Rhythms 5. Pharmacology Hypnotics: Basic Mechanisms and Pharmacology Hypnotics: Efficacy and Adverse Effects Stimulants: Basic Mechanisms and Pharmacology Stimulants: Efficacy and Adverse Effects Drugs Which Disturb Sleep and Wakefulness 6. Psychobiology and Dreaming Approaches to the Study of Dream Content: Methods Measures
4,558 citations
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
Abstract: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum (ER), where they fold and assemble. Only properly assembled proteins advance from the ER to the cell surface. To ascertain fidelity in protein folding, cells regulate the protein-folding capacity in the ER according to need. The ER responds to the burden of unfolded proteins in its lumen (ER stress) by activating intracellular signal transduction pathways, collectively termed the unfolded protein response (UPR). Together, at least three mechanistically distinct branches of the UPR regulate the expression of numerous genes that maintain homeostasis in the ER or induce apoptosis if ER stress remains unmitigated. Recent advances shed light on mechanistic complexities and on the role of the UPR in numerous diseases.
4,468 citations
Book•
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TL;DR: The brain's default state: self-organized oscillations in rest and sleep, and perturbation of the default patterns by experience.
Abstract: Prelude. Cycle 1. Introduction. Cycle 2. Structure defines function. Cycle 3. Diversity of cortical functions is provided by inhibition. Cycle 4. Windows on the brain. Cycle 5. A system of rhythms: from simple to complex dynamics. Cycle 6. Synchronization by oscillation. Cycle 7. The brain's default state: self-organized oscillations in rest and sleep. Cycle 8. Perturbation of the default patterns by experience. Cycle 9. The gamma buzz: gluing by oscillations in the waking brain. Cycle 10. Perceptions and actions are brain state-dependent. Cycle 11. Oscillations in the "other cortex:" navigation in real and memory space. Cycle 12. Coupling of systems by oscillations. Cycle 13. The tough problem. References.
4,266 citations
Journal Article•
3,696 citations
TL;DR: High-density recordings of field activity in animals and subdural grid recordings in humans can provide insight into the cooperative behaviour of neurons, their average synaptic input and their spiking output, and can increase the understanding of how these processes contribute to the extracellular signal.
Abstract: Neuronal activity in the brain gives rise to transmembrane currents that can be measured in the extracellular medium. Although the major contributor of the extracellular signal is the synaptic transmembrane current, other sources — including Na+ and Ca2+ spikes, ionic fluxes through voltage- and ligand-gated channels, and intrinsic membrane oscillations — can substantially shape the extracellular field. High-density recordings of field activity in animals and subdural grid recordings in humans, combined with recently developed data processing tools and computational modelling, can provide insight into the cooperative behaviour of neurons, their average synaptic input and their spiking output, and can increase our understanding of how these processes contribute to the extracellular signal.
3,366 citations