Sleep is a phenomenon of astounding complexity, which makes it difficult to understand and even define unequivocally. It can be viewed as behaviour, a brain state and a process, which are intricately interrelated, and manifest themselves at many distinct spatio-temporal scales. Sleep is regulated by circadian time, preceding sleep-wake history, and, while asleep, the brain switches periodically between two markedly different states – NREM sleep and REM sleep, which are distinguished by specific types of brain activity. Specifically, a closer look at NREM sleep reveals that it is characterised by a regular occurrence of local and global slow cortical oscillations, visible at the level of the EEG as slow waves. Throughout NREM sleep, especially during its lighter stages and towards a transition into REM sleep, another type of activity is apparent, so-called sleep spindles. These involve the thalamus and through dynamic cortico-thalamic interactions emerge quasi-independently at specific brain locations and never across the whole brain at once. In contrast, during REM sleep the brain is about as active as it is in waking, and the EEG in both humans and animals is dominated by theta- and faster rhythms, which arise from bidirectional interactions of cortical, hippocampal and subcortical networks. Are all these sleep-related phenomena related to each other and what is the functional meaning of the overall complexity of the sleep process?
Our aim is to understand the mechanisms governing the spatio-temporal dynamics of brain activity during sleep. This will help us to understand not only what sleep is, but also why it is necessary.
14.03.18 "Cortical region-specific sleep homeostasis in mice: effects of time of day and waking experience" by Mathilde Guillaumin, Laura McKillop, Nanyi Cui, Simon Fisher, Russell Foster, Maarten de Vos, Stuart Peirson, Peter Achermann and Vlad Vyazovskiy is accepted for publication in SLEEP
22.02.18. "Effects of ageing on cortical neural dynamics and local sleep homeostasis in mice" by L. E. McKillop, S. P. Fisher, N. Cui, S. N. Peirson, R. G. Foster, K. A. Wafford and V.V. Vyazovskiy has been accepted in The Journal of Neuroscience.
22.01.18. "Light and Cognition: Roles for Circadian Rhythms, Sleep and Arousal" by Angus Fisk, Shu Tam, Laurence Brown, Vladyslav Vyazovskiy, David Bannerman and Stuart Peirson" has been accepted in Frontiers in Neurology, section Sleep and Chronobiology.
24.08.17. "The interplay between long- and short-range temporal correlations shapes cortex dynamics across vigilance states." by Meisel C, Klaus A, Vyazovskiy VV and Plenz D. has been accepted in the Journal of Neuroscience
05.03.17. "Sleep homeostasis, habits and habituation" by Vyazovskiy VV, Walton ME, Peirson SN, Bannerman DM. has been accepted for publication in Current Opinion in Neurobiology.
04.02.17. "Constant Light Desynchronises Olfactory versus Object and Visuospatial Recognition Memory Performance" by Tam SK, Hasan S, Choi HMC, Brown LA, Jagannath A, Hughes S, Hankins MW, Foster RG, Vyazovskiy VV, Bannerman DM and Peirson SN. has been accepted in The Journal of Neuroscience.
25.01.17. "Differences in electroencephalographic non-rapid-eye movement sleep slow-wave characteristics in aged mice between young and old mice." by Panagiotou M, Vyazovskiy VV, Meijer JH and Deboer T. has been accepted in Scientific Reports.
10.01.17. "Different effects of sleep deprivation and torpor on EEG slow wave characteristics in Djungarian hamsters" by Vladyslav Vyazovskiy, Svitlana Palchykova, Peter Achermann, Irene Tobler and Tom Deboer is accepted for publication in Cerebral Cortex
10.01.17. European Sleep Research Society Sleep Science School "Neural Networks in Sleep": applications invited.
02.12.16. "Learning by association in plants" by Monica Gagliano, Vladyslav V. Vyazovskiy, Alexander A. Borbély, Mavra Grimonprez & Martial Depczynski is published in Scientific Reports
17.10.16. "Stereotypic wheel running decreases cortical activity in mice" is published in Nature Communications
11.10.16-. Oxford Online Programme in Sleep Medicine hosted by the Sleep and Circadian Neuroscience Institute (SCNi), University of Oxford is launched
07.10.16. VV: "Local cortical slow waves and sleep homeostasis": presentation at Slow Waves Dynamics Workshop, EITN, Paris
13-16.09.16. VV: "Spatio-temporal dynamics of brain activity during sleep", 23rd Congress of the European Sleep Research Society, Bologna, Italy
12.09.16. "Sleep and serotonin modulate paracapsular nitric oxide synthase expressing neurons of the amygdala" by Marco Bocchio, Simon P Fisher, Gunes Unal, Tommas J Ellender, Vladyslav V Vyazovskiy and Marco Capogna has been accepted for publication in eNeuro
07.09.16. "Stereotypic wheel running decreases cortical activity in mice" by Fisher SP, Cui N, McKillop LM, Gemignani J, Bannerman DM, Oliver PL, Peirson SN, Vyazovskiy VV is accepted for publication in Nature Communications
01.09.16. Cristina Blanco Duque and Alberto Lazari start DPhil projects in collaboration with Heidi Johansen-Berg and David Bannerman
01.09.16. Christopher Thomas joins the group as DPhil Student in the BBSRC Interdisciplinary Biosciences Doctoral Training Centre
01.07.16. VV: Waking behaviour, cortical states and sleep homeostasis, Satellite Symposium of the European Sleep Research Society, FENS Forum 2016, Copenhagen, Denmark
28.06.16. Laura McKillop is awarded a travel grant from the European Sleep Research Society to attend the 23rd ESRS congress in Bologna, Italy
24.06.16. 11 MINUTES OF SLEEP IN PISA: Hot topics in Sleep Physiology and Health Care
12-14.05.16. 1st International Conference on Sleep Spindling, Budapest Hungary
22.04.16. "Melanopsin regulates both sleep-promoting and arousal-promoting responses to light" by Pilorz V, Tam SK, Hughes S, Pothecary CA, Jagannath A, Hankins MW, Bannerman DM, Lightman SL, Vyazovskiy VV, Nolan PM, Foster RG, Peirson SN.is accepted for publication in PLoS Biology
13.02.16. VV: What’s going on inside the sleeping brain, The 13th Oxford Brain day: The Sleeping Brain
02.16 “Unravelling the complexity of sleep”, Phenotype magazine
15.03.16. “Could humans hibernate?” The Conversation
22.12.15. "Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations" by Sela Y, Vyazovskiy VV, Cirelli C, Tononi G, Nir Y. has been accepted for publication in SLEEP.
20.11.15. "Neuroscience. Mapping the birth of the sleep connectome", Comment on "Cells of a common developmental origin regulate REM/non-REM sleep and wakefulness in mice." published in Science
27.10.15. Editorial "Banking sleep and biological sleep need: Commentary on Arnal et al. Benefits of Sleep Extension on Sustained Attention and Sleep Pressure Before and During Total Sleep Deprivation and Recovery" has been accepted for publication in SLEEP.
15-17.10.15. "Local sleep and brain plasticity", Berner Schlaf-Wach-Tage, Bern, Switzerland
17-18.09.15. VV: "The dynamics of sleep process in time and space", Doctoral Program Brain and Mind, Helsinki, Finland
12.09.15. VV: "Sleep Homeostasis: local and global aspects", Keynote lecture at the Korean Sleep Society conference, Seoul, South Korea
2-6.08.15. VV: "The temporal dynamics of waking and sleep: from single neurons to behaviour", European Biological Rhythms Society (EBRS)/World Congress of Chronobiology (WCC), joint EBRS/ESRS symposium, Manchester, UK
01.06.15 A three-year Postdoctoral Research Scientist in Sleep Neurobiology position is available. Applications are accepted until 01.07.2015
22.04.15 VVlab established a collaboration with Advanced Concepts Team of the European Space Agency through Ariadna initiative
07.04.15 A new visiting researcher Dr Tomoko Yamagata joins our group.
03.04.15 "Long-term history and immediate preceding state affect EEG slow wave characteristics at NREM sleep onset in C57BL/6 mice" by Cui N, Mckillop LE, Fisher SP, Oliver PL, Vyazovskiy VV. has been published in Arch Ital Biol.
30.03.15. VV has been awarded a title of Associate Professor
25.03.15. Simon Fisher has been selected a recipient of a Sleep Research Society Abstract Merit Based Award
24.02.15. "Lempel-Ziv complexity of cortical activity during sleep and waking in rats" by D. Abásolo, S. Simons, R. Morgado da Silva, G. Tononi and V.V.Vyazovskiy has been accepted for publication in The Journal of Neurophysiology
01.11.14. Our application (VV and Reto Huber) to the Oxford-McGill-ZNZ Partnership in the Neurosciences grant has been successful
01.11.14. Local Sleep Taking Care of High-Maintenance Cortical Circuits under Sleep Restriction: Editorial by Simon Fisher and Vladyslav Vyazovskiy in the last issue of SLEEP
05.11.14. Symposium "11 MINUTES OF SLEEP: an open window on brain plasticity, cortical functions and consciousness", Pisa, Italy, 5th November, 2014
01.08.14 "The Dynamics of Cortical Neuronal Activity in the First Minutes after Spontaneous Awakening in Rats and Mice" by
VV, N. Cui, AV Rodriguez, C Funk, C Cirelli and G Tononi in the August 2014 issue of SLEEP
21.07.14 Dr Simon Fisher joins our team as a Postdoctoral Researcher
16.07.14 VV is selected as a Travel Awardee for the 2014 American College of Neuropsychopharmacology Annual Meeting in Phoenix, Arizona, 7-11.12.2014
14.07.14 The proposal entitled, “Local and Global Sleep regulation, Cellular Functions of Sleep and Neuropsychiatric Disorders” has been accepted as a Panel at the 53rd American College of Neuropsychopharmacology Annual Meeting in Phoenix, Arizona, 7-11.12.2014. (Chair: R. Benca, Presenters: V.V. Vyazovskiy, T. Kilduff, A. Krystal, R. Benca)
02.07.14 Our symposium proposal entitled “Sleep, Brain State and Sensory Processing” has been accepted for inclusion in the British Neuroscience Association 2015: Festival of Neuroscience (Edinburgh, UK, 12-15.04.2015). Speakers include V.V. Vyazovskiy, M. Sanchez-Vives, K. Harris, M. Carandini, A. Thiele
26.06.14 VV: Homeostatic regulation of sleep and its regional aspects. Nuffield Department of Clinical Neurosciences Monthly Seminars. listen podcast
25.06.14 Our abstract "EEG slow-wave characteristics in sleep after daily torpor in Djungarian hamsters" by VV Vyazovskiy, I Tobler and T Deboer has been accepted for Oral presentation at the 22nd Congress of the European Sleep Research Society (Tallinn, Estonia, 16-20.09.2014)
16.06.14 VV and Foster RG: Sleep: A Biological Stimulus from Our Nearest Celestial Neighbor? Curr Biol 2014
08.05.14 VV: ‘The temporal dynamics of sleep: cortical mechanisms and functional significance’ (Room B15, UCL Anatomy, Gower Street, 5.00 pm)
17.03.14 VV: "Spatio-temporal complexity of brain activity during sleep: functional significance and implications for sleep regulation", The European Winter Conference on Brain Research | The European Brain and Behaviour Society, Brides-les-Bains, France
26.03.14 VV: "Global Sleep and the Single Neuron: Spatio-Temporal Complexity and the Function of Sleep", The 5th Oxford Neuroscience Symposium, Oxford, UK
04.07.14 9th Federation European Neurosciences Societies (FENS) Forum of Neuroscience, Sattelite Symposium of the European Sleep Research Society "Understanding Sleep: Novel Perspectives in Neurosciences", Milan, Italy.
01.12.13 VV and the team move to the University of Oxford, where we join the newly established Sleep and Circadian Neuroscience Institute.
22.11.13 VV: "Sleep homeostasis and the function of sleep", keynote lecture, XIV Brazilian Sleep Association Meeting, Rio de Janeiro, Brazil.
12.11.13 "NREM and REM sleep: complementary roles in recovery after wakefulness" by Vladyslav Vyazovskiy and Alessio Delogu has been accepted for publication in The Neuroscientist.
07.07.13 VV: "Homeostatic sleep regulation and the function of sleep", at Special Session "Sleep and Higher Order Brain Functions", The 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, in conjunction with 52nd Annual Conference of Japanese Society for Medical and Biological Engineering, Osaka, Japan.
14.06.13 VV and Kenneth Harris on Neuropod Podcast: Restful Repair
11.06.13 VV's presentation at the last SLEEP meeting, Baltimore, USA, June 2nd-5th 2013: Mechanisms and functions of local sleep: Implications for sleep homeostasis
20.05.13 "Sleeping in sync" by Jennie Vallis on the cover of the June issue of Nature Reviews Neuroscience.
02.05.13 "Sleep and the single neuron: the role of global slow oscillations in individual cell rest" by Vladyslav V. Vyazovskiy and Kenneth D. Harris has been accepted for publication in Nature Reviews Neuroscience, and will appear in the June issue. It is now available online.
11.04.13 Professor Bryan Vila from Washington State University (USA) gives a lecture "Tired Cops Research: Results from High-Fidelity Simulations of Hazardous Operational Tasks". Sleep, Chronobiology and Addiction Research Group seminar, University of Surrey, Wednesday, 17.04.13, 15:00, room 06DK02.
02.04.13 VV: "Mechanisms and functions of sleep homeostasis", Conference "EEG Rhythms of Health and Disease States", May 16-18, 2013, Cardiff, UK
15.03.13 Symposium “Local Sleep: Its Origin and Function” proposed by Reto Huber and Yuval Nir has been accepted for presentation at SLEEP 2013 27th Annual Meeting of the Associated Professional Sleep Societies, LLC, held June 1-5, 2013, in Baltimore, Maryland. The session will take place on Tuesday, June 4, 2013, from 10:20am – 12:20pm. Speakers: VV, Reto Huber, Yuval Nir and Hans van Dongen.
12.01.13 VV: "Local and global dynamics of neuronal activity in the neocortex: implications for the function of sleep.", Department of Computing, University of Surrey, 06.02.13, 2:15 pm, room 39 BB 02.
14.12.12 VV has been invited as a speaker at XIV Brazilian Sleep Association Bi-annual Meeting, that takes place in Rio de Janeiro, Brazil, November 21st - 24th, 2013
13.12.12 Vladyslav Vyazovskiy, "In quest for the function of sleep: from single cells to system level", Workshop "Genes and Behaviour", University of Surrey - Guildford.
10.12.12 Dr. Alessio Delogu from MRC Centre for Developmental Neurobiology at King's College London will be presenting a talk titled: "Regulation of diurnal rhythms: new light from developmental studies" on December 10th at 1:00 pm in 13 AY 02.
06.12.12 Vyazovskiy V.V and Tobler I. "The temporal structure of behaviour and sleep homeostasis" appeared today in PLoS One.
29.11.12 VV application to the 4‐year BBSRC Industrial CASE studentship Competition (together Eli Lilly) has been successful! The PhD position will be advertised soon.
29.11.12 VV is invited to give a lecture at the 35th Annual Conference of IEEE Engineering in Medicine and Biology Society in Osaka, Japan, July 3-7, 2013.
25.10.12 Paper accepted for publication in PLOS ONE: "The temporal structure of behaviour and sleep homeostasis" by Vladyslav V. Vyazovskiy and Irene Tobler.
22.10.12 Julia Harris, University College London, David Attwell Lab, gives a lecture at the University of Surrey on "Brain energetics: energy use and information processing in the white and grey matter": 07.11.2012, 11am, 06 DK 02
16.10.12 Prof. Debra Skene: How does your body know what time it is? Café Scientifique, London, 6:30 pm – 8:00 pm, Monday 22.10.2012
15.10.12 SFN meeting 2012: "Pharmacogenetic and optogenetic induction of local tonic cortical activity in anesthetized mice" by C.M. Funk, Y. Nir, V.V. Vyazovskiy, M. Mieda, T. Sakurai, O. Yizhar, C. Cirelli and G. Tononi
10.10.12 Colloquium: Current Topics in Sleep and Chronobiology Research, University of Zurich, Switzerland, 02.11.2012: "Sleep homeostasis, neuronal synchrony and single-cell rest" by Vladyslav Vyazovskiy
04.10.12 Paper accepted for publication in Journal of Sleep Research: "Prolonged wakefulness alters neuronal responsiveness to local electrical stimulation of the neocortex in awake rats" by Vladyslav V. Vyazovskiy, Umberto Olcese, Chiara Cirelli and Giulio Tononi
01.10.12 new member of VVlab, PhD student Nanyi Cui.
10.09.12 VV's presentation at the last ESRS meeting (Paris, September 4-8th, 2012): Local sleep: insights from multiunit recordings during sleep and waking
Sleep and serotonin modulate paracapsular nitric oxide synthase expressing neurons of the amygdala
Bocchio M, Fisher SP, Unal G, Ellender TJ, Vyazovskiy VV, Capogna M
Unraveling the roles of distinct neuron types is a fundamental challenge to understand brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons is only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). Notably, these cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch clamp recordings from nNOS+ neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+ neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+ neurons were activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin (5-HT) neurons, which are involved in sleep-wake regulation, innervate nNOS+ neurons. Bath application of 5-HT hyperpolarizes nNOS+ neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+ cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links between mood, sleep deprivation and 5-HT, the recruitment of paracapsular nNOS+ neurons following high sleep pressure may represent a novel mechanism in emotional regulation.
Stereotypic wheel running decreases cortical activity in mice
Nature Communications, 2016
Fisher SP, Cui N, McKillop LM, Gemignani J, Bannerman DM, Oliver PL, Peirson SN, Vyazovskiy VV.
Prolonged wakefulness is thought to gradually increase ‘sleep need’ and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours.
Lempel-Ziv complexity of cortical activity during sleep and waking in rats
The Journal of Neurophysiology, 2015
D. Abásolo, S. Simons, R. Morgado da Silva, G. Tononi, and V.V. Vyazovskiy
Understanding the dynamics of brain activity manifested in the electroencephalogram (EEG), local-field potentials (LFP) and neuronal spiking is essential for explaining their underlying mechanisms and physiological significance. Much has been learned about sleep regulation using conventional EEG power spectrum, coherence and period-amplitude analyses, which focus primarily on frequency and amplitude characteristics of the signals and on their spatio-temporal synchronicity. However, little is known about the effects of ongoing brain state or preceding sleep-wake history on the nonlinear dynamics of brain activity. Recent advances in developing novel mathematical approaches for investigating temporal structure of brain activity based on such measures, as Lempel-Ziv complexity (LZC) can provide insights that go beyond those obtained with conventional techniques of signal analysis. Here we used extensive data sets obtained in spontaneously awake and sleeping adult male laboratory rats, as well as during and after sleep deprivation, to perform a detailed analysis of cortical local field potential (LFP) and neuronal activity with LZC approach. We found that activated brain states - waking and rapid-eye movement (REM) sleep are characterized by higher LZC as compared to non-rapid-eye movement (NREM) sleep. Notably, LZC values derived from the LFP were especially low during early NREM sleep after sleep deprivation, and towards the middle of individual NREM sleep episodes. We conclude that LZC is an important and yet largely unexplored measure with a high potential for investigating neurophysiologic mechanisms of brain activity in health and disease.
NREM and REM sleep: Complementary roles in recovery after wakefulness
The Neuroscientist, 2014
Vyazovskiy VV, Delogu A
The overall function of sleep is hypothesised to provide “recovery” after preceding waking activities, thereby ensuring optimal functioning during subsequent wakefulness. However, the functional significance of the temporal dynamics of sleep, manifested in the slow homeostatic process and the alternation between non-rapid eye movement (NREM) and REM sleep remains unclear. We propose that NREM and REM sleep have distinct and complementary contributions to the overall function of sleep. Specifically, we suggest that cortical slow oscillations, occurring within specific functionally interconnected neuronal networks during NREM sleep enable information processing, synaptic plasticity and prophylactic cellular maintenance (“recovery process”). In turn, periodic excursions into an activated brain state – REM sleep – appear to be ideally placed to perform “selection” of brain networks, which have benefited from the process of “recovery”, based on their offline performance. Such two-stage modus operandi of the sleep process would ensure that its functions are fulfilled according to the current need and in the shortest time possible. Our hypothesis accounts for the overall architecture of normal sleep and opens up new perspectives for understanding pathological conditions associated with abnormal sleep patterns.
Vyazovskiy VV, Cui N, Rodriguez AV, Funk C, Cirelli C, Tononi G
Study Objective: Upon awakening from sleep, a fully awake brain state is not re-established immediately, but the origin and physiological properties of the distinct brain state during the first minutes after awakening are unclear. To investigate whether neuronal firing immediately upon arousal is different from the remaining part of the waking episode, we recorded and analysed the dynamics of cortical neuronal activity in the first 15 minutes after spontaneous awakenings in freely moving rats and mice. Design: Intracortical recordings of the local field potential and neuronal activity in freely-moving mice and rats. Setting: Basic sleep research laboratory. Patients or Participants: WKY adult male rats, C57BL/6 adult male mice. Interventions: N/A. Measurements and Results: In both species the average population spiking activity upon arousal was initially low, though substantial variability in the dynamics of firing activity was apparent between individual neurons. A distinct population of neurons was found that was virtually silent in the first minutes upon awakening. The overall lower population spiking initially after awakening was associated with the occurrence of brief periods of generalized neuronal silence (OFF periods), whose frequency peaked immediately after awakening and then progressively declined. OFF periods incidence upon awakening was independent of ongoing locomotor activity but was sensitive to immediate preceding sleep/wake history. Notably, in both rats and mice if sleep before a waking episode was enriched in REM sleep, the incidence of OFF periods was initially higher as compared to those waking episodes preceded mainly by NREM sleep. Conclusion: We speculate that an intrusion of sleep-like patterns of cortical neuronal activity into the wake state immediately after awakening may account for some of the changes in the behaviour and cognitive function typical for sleep inertia.
Curr Top Behav Neurosci, 2014
Vyazovskiy VV, Faraguna U
In the last decades a substantial knowledge about sleep mechanisms has been accumulated. However, the function of sleep still remains elusive. The difficulty with unraveling sleep’s function may arise from the lack of understanding of how the multitude of processes associated with waking and sleep – from gene expression and single neuron activity to the whole brain dynamics and behaviour – functionally and mechanistically relate to each other. Therefore, novel conceptual frameworks, which integrate and take into account the variety of phenomena occurring during waking and sleep at different levels, will likely lead to advances in our understanding of the function of sleep, above and beyond of what merely descriptive or correlative approaches can provide. One such framework, the synaptic homeostasis hypothesis, focuses on wake- and sleep- dependent changes in synaptic strength. The core claim of this hypothesis is that learning and experience during wakefulness are associated with a net increase in synaptic strength. In turn, the proposed sleep’s function is to provide synaptic renormalization, which has important implications with respect to energy needs, intracranial space, metabolic supplies, and, importantly, enables further plastic changes. In this article we review the empirical evidence for this hypothesis, which was obtained at several levels – from gene expression and cellular excitability to structural synaptic modifications and behavioural outcomes. We conclude that although the mechanisms behind the proposed role of sleep in synaptic homeostasis are undoubtedly complex, this conceptual framework offers a unique opportunity to provide mechanistic and functional explanation for many previously disparate observations, and define future research strategies.
Vyazovskiy VV & Harris KD
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.
The temporal structure of behaviour and sleep homeostasis
PLoS One, 2012
Vyazovskiy VV & Tobler I
The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states – NREM and REM sleep, which occur, in rodents, on a time scale of ~5-10 minutes. Neither the mechanisms underlying the time constants of these two processes – the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism.
Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G.
In an awake state, neurons in the cerebral cortex fire irregularly and electroencephalogram (EEG) recordings display low-amplitude, high-frequency fluctuations. During sleep, neurons oscillate between 'on' periods, when they fire as in an awake brain, and 'off' periods, when they stop firing altogether and the EEG displays high-amplitude slow waves. However, what happens to neuronal firing after a long period of being awake is not known. Here we show that in freely behaving rats after a long period in an awake state, cortical neurons can go briefly 'offline' as in sleep, accompanied by slow waves in the local EEG. Neurons often go offline in one cortical area but not in another, and during these periods of 'local sleep', the incidence of which increases with the duration of the awake state, rats are active and display an 'awake' EEG. However, they are progressively impaired in a sugar pellet reaching task. Thus, although both the EEG and behaviour indicate wakefulness, local populations of neurons in the cortex may be falling asleep, with negative consequences for performance.
Prolonged wakefulness alters neuronal responsiveness to local electrical stimulation of the neocortex in awake rats
Journal of Sleep Research, 2012
Vyazovskiy VV, Olcese U, Cirelli C, Tononi G
Prolonged wakefulness or a lack of sleep lead to cognitive deficits, but little is known about the underlying cellular mechanisms. We recently found that sleep deprivation affects spontaneous neuronal activity in the neocortex of sleeping and awake rats. While it is well known that synaptic responses are modulated by ongoing cortical activity, it remains unclear whether prolonged waking affects responsiveness of cortical neurons to incoming stimuli. By applying local electrical microstimulation to the frontal area of the neocortex, we found that after a 4-hour period of waking the initial neuronal response in the contralateral frontal cortex was stronger and more synchronous, and was followed by a more profound inhibition of neuronal spiking as compared to the control condition. These changes in evoked activity suggest increased neuronal excitability and indicate that after staying awake cortical neurons become transiently bistable. We propose that some of the detrimental effects of sleep deprivation may be a result of altered neuronal responsiveness to incoming intrinsic and extrinsic inputs.
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