Dr Vladyslav Vyazovskiy

Biography

Research Interests

The longer we are awake, the deeper and more consolidated is our subsequent sleep. On the other hand, the shorter and more fragmented is our sleep, the more difficult it is for us to maintain wakefulness and stable cognitive performance the next day. This relationship between wakefulness and subsequent sleep becomes especially apparent after sleep deprivation or during chronic sleep restriction, which is experienced by millions of people in our society, as well as in multiple neurological, respiratory and other chronic diseases. Invariably, poor sleep leads to fatigue, sleepiness, marked cognitive deficits and impaired mood. The crucial question is what happens to the brain after a period of being awake or asleep, and where in the brain and why do these changes occur?

My main research interest is to clarify the cortical neuronal mechanisms underlying sensory, behavioural and cognitive deficits that arise as a result of sleep deprivation.

My previous work has been devoted to elucidating cortical neuronal and network mechanisms of sleep regulation. We have recently shown (Vyazovskiy et al., Nature, 2011) that following sleep deprivation cortical neurons in awake freely moving rats tend to go briefly ‘OFF line’ as they do in sleep, and that such “local sleep” was associated with an impairment in a behavioural task. This study provided the most appealing evidence yet for a currently highly influential view that sleep is a property of local neuronal assemblies, has a role in synaptic plasticity, and affects cognition (Tononi and Cirelli, 2003; Krueger et al., 2008).

The study reported in Nature was a logical continuation of my earlier work, in which I addressed the cellular mechanisms of sleep homeostasis by performing extracellular multi- and single-unit recordings from the neocortex of awake and sleeping rats. Specifically, my work performed at the University of Wisconsin-Madison in the Laboratory of Giulio Tononi and Chiara Cirelli showed that the patterns of neuronal activity in the neocortex are determined by preceding sleep/wake history (Vyazovskiy et al., Neuron, 2009).

This work was preceded by studies, performed at the Institute of Pharmacology and Toxicology, University of Zurich in the Laboratory of Irene Tobler and Alexander Borbèly, showing how specific sensory stimulation led to changes in sleep slow-wave activity, that were confined to those brain areas most affected by sensory stimulation (Vyazovskiy et al., J Sleep Res, 2000).

During my postdoctoral studies, I led the effort in providing comprehensive experimental evidence for investigating synaptic mechanisms of sleep homeostasis. This work, published in Nature Neuroscience, J Neuroscience, Cerebral Cortex and Sleep provided conclusive evidence in support of the hypothesis that being awake is associated with increased cortical effective connectivity, while sleep serves synaptic downscaling (Tononi and Cirelli, 2006). Finally, I and colleagues have also performed a challenging experiment, which demonstrated that in chronically sleep-deprived rats, slower EEG activity, including SWA (0.5–4 Hz) or low theta (5–7 Hz) activity, leaks into periods of behavioural waking, and it does so in a region-specific manner (Vyazovskiy, Leemburg et al,. PNAS, 2009).

Several specific questions remain unanswered and are the primary goals of my future research.  It is unclear at what level sleep need accumulates and where sleep is initiated: e.g. individual neurons, local or distributed neuronal populations, cortical or subcortical regions, or specific neuronal subtypes?  Moreover, it is still unknown which molecular, cellular and network mechanisms underlie the need for sleep, and what happens in the brain during waking that necessitates the occurrence of sleep.  Finally, very little is known about how the changes in brain activity incurred during normal waking or sleep deprivation translate in the well-known behavioral and cognitive deficits.  I plan to use a suite of appropriate state-of-the-art methodologies, including electrophysiology, sensory stimulation, behavioural testing and molecular tools, to investigate neuronal mechanisms underlying behavioural, sensory and cognitive deficits incurred after sleep deprivation.

Publications

1. Bellesi M, Vyazovskiy VV, Tononi G, Cirelli C, Conti F. Reduction of EEG theta power and changes in motor activity in rats treated with ceftriaxone. PLoS One 2012;7(3):e34139.
2. Vyazovskiy VV, Olcese U, Hanlon EC, Nir Y, Cirelli C, Tononi G. Local sleep in awake rats. Nature 2011;472(7344):443-7.
3. Vyazovskiy VV, Cirelli C, Tononi G. Electrophysiological correlates of sleep homeostasis in freely behaving rats. Progress in brain research 2011;193:17-38.
4. Nir Y, Staba RJ, Andrillon T, et al. Regional slow waves and spindles in human sleep. Neuron 2011;70(1):153-69.
5. Hanlon EC, Vyazovskiy VV, Faraguna U, Tononi G, Cirelli C. Synaptic potentiation and sleep need: clues from molecular and electrophysiological studies. Current topics in medicinal chemistry 2011;11(19):2472-82.
6. Leemburg S, Vyazovskiy VV, Olcese U, Bassetti CL, Tononi G, Cirelli C. Sleep homeostasis in the rat is preserved during chronic sleep restriction. Proceedings of the National Academy of Sciences of the United States of America 2010;107(36):15939-44.
7. Faraguna U, Nelson A, Vyazovskiy VV, Cirelli C, Tononi G. Unilateral cortical spreading depression affects sleep need and induces molecular and electrophysiological signs of synaptic potentiation in vivo. Cereb Cortex 2010;20(12):2939-47.
8. Vyazovskiy VV, Tobler I, Cirelli C, Tononi G. Author's reply to "cerebral metabolism and sleep homeostasis: a comment on Vyazovskiy et al.". Brain research bulletin 2009;80(6):443-5.
9. Vyazovskiy VV, Olcese U, Lazimy YM, et al. Cortical firing and sleep homeostasis. Neuron 2009;63(6):865-78.
10. Vyazovskiy VV, Faraguna U, Cirelli C, Tononi G. Triggering slow waves during NREM sleep in the rat by intracortical electrical stimulation: effects of sleep/wake history and background activity. Journal of neurophysiology 2009;101(4):1921-31.
11. Hanlon EC, Faraguna U, Vyazovskiy VV, Tononi G, Cirelli C. Effects of skilled training on sleep slow wave activity and cortical gene expression in the rat. Sleep 2009;32(6):719-29.
12. Dash MB, Douglas CL, Vyazovskiy VV, Cirelli C, Tononi G. Long-term homeostasis of extracellular glutamate in the rat cerebral cortex across sleep and waking states. The Journal of neuroscience : the official journal of the Society for Neuroscience 2009;29(3):620-9.
13. Winsky-Sommerer R, Knapman A, Fedele DE, et al. Normal sleep homeostasis and lack of epilepsy phenotype in GABA A receptor alpha3 subunit-knockout mice. Neuroscience 2008;154(2):595-605.
14. Vyazovskiy VV, Tobler I. Handedness leads to interhemispheric EEG asymmetry during sleep in the rat. Journal of neurophysiology 2008;99(2):969-75.
15. Vyazovskiy VV, Cirelli C, Tononi G, Tobler I. Cortical metabolic rates as measured by 2-deoxyglucose-uptake are increased after waking and decreased after sleep in mice. Brain research bulletin 2008;75(5):591-7.
16. Vyazovskiy VV, Cirelli C, Pfister-Genskow M, Faraguna U, Tononi G. Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep. Nature neuroscience 2008;11(2):200-8.
17. Jones SG, Vyazovskiy VV, Cirelli C, Tononi G, Benca RM. Homeostatic regulation of sleep in the white-crowned sparrow (Zonotrichia leucophrys gambelii). BMC neuroscience 2008;9:47.
18. Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C. A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. The Journal of neuroscience : the official journal of the Society for Neuroscience 2008;28(15):4088-95.
19. Winsky-Sommerer R, Vyazovskiy VV, Homanics GE, Tobler I. The EEG effects of THIP (Gaboxadol) on sleep and waking are mediated by the GABA(A)delta-subunit-containing receptors. The European journal of neuroscience 2007;25(6):1893-9.
20. Vyazovskiy VV, Tobler I, Winsky-Sommerer R. Alteration of behavior in mice by muscimol is associated with regional electroencephalogram synchronization. Neuroscience 2007;147(3):833-41.
21. Vyazovskiy VV, Riedner BA, Cirelli C, Tononi G. Sleep homeostasis and cortical synchronization: II. A local field potential study of sleep slow waves in the rat. Sleep 2007;30(12):1631-42.
22. Vyazovskiy VV, Achermann P, Tobler I. Sleep homeostasis in the rat in the light and dark period. Brain research bulletin 2007;74(1-3):37-44.
23. Riedner BA, Vyazovskiy VV, Huber R, et al. Sleep homeostasis and cortical synchronization: III. A high-density EEG study of sleep slow waves in humans. Sleep 2007;30(12):1643-57.
24. Douglas CL, Vyazovskiy V, Southard T, et al. Sleep in Kcna2 knockout mice. BMC biology 2007;5:42.
25. Vyazovskiy VV, Ruijgrok G, Deboer T, Tobler I. Running wheel accessibility affects the regional electroencephalogram during sleep in mice. Cereb Cortex 2006;16(3):328-36.
26. Vyazovskiy VV, Kopp C, Wigger E, Jones ME, Simpson ER, Tobler I. Sleep and rest regulation in young and old oestrogen-deficient female mice. Journal of neuroendocrinology 2006;18(8):567-76.
27. Vyazovskiy VV, Tobler I. Theta activity in the waking EEG is a marker of sleep propensity in the rat. Brain research 2005;1050(1-2):64-71.
28. Vyazovskiy VV, Tobler I. Regional differences in NREM sleep slow-wave activity in mice with congenital callosal dysgenesis. Journal of sleep research 2005;14(3):299-304.
29. Vyazovskiy VV, Kopp C, Bosch G, Tobler I. The GABAA receptor agonist THIP alters the EEG in waking and sleep of mice. Neuropharmacology 2005;48(5):617-26.
30. Vyazovskiy VV, Welker E, Fritschy JM, Tobler I. Regional pattern of metabolic activation is reflected in the sleep EEG after sleep deprivation combined with unilateral whisker stimulation in mice. The European journal of neuroscience 2004;20(5):1363-70.
31. Vyazovskiy VV, Achermann P, Borbely AA, Tobler I. The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice. Archives italiennes de biologie 2004;142(4):511-23.
32. Vyazovskiy V, Achermann P, Borbely AA, Tobler I. Interhemispheric coherence of the sleep electroencephalogram in mice with congenital callosal dysgenesis. Neuroscience 2004;124(2):481-8.
33. Vyazovskiy VV, Deboer T, Rudy B, Lau D, Borbely AA, Tobler I. Sleep EEG in mice that are deficient in the potassium channel subunit K.v.3.2. Brain research 2002;947(2):204-11.
34. Vyazovskiy VV, Borbely AA, Tobler I. Interhemispheric sleep EEG asymmetry in the rat is enhanced by sleep deprivation. Journal of neurophysiology 2002;88(5):2280-6.
35. Vyazovskiy V, Borbely AA, Tobler I. Unilateral vibrissae stimulation during waking induces interhemispheric EEG asymmetry during subsequent sleep in the rat. Journal of sleep research 2000;9(4):367-71.
36. Deboer T, Vyazovskiy VV, Tobler I. Long photoperiod restores the 24-h rhythm of sleep and EEG slow-wave activity in the Djungarian hamster (Phodopus sungorus). Journal of biological rhythms 2000;15(5):429-36.

Book chapters
1. Vyazovskiy V.V., Olcese U., Tononi G. " Investigating Sleep Homeostasis with Extracellular Recording of Multiunit Activity from the Neocortex in Freely Behaving Rats" In Fellin, T. and Halassa, M. (Eds), Neuronal Networks Analysis, Concepts and Experimental Approaches, Neuromethods Series, Vol. 67, Springer (2012).

I am looking for a self-funded PhD student to work on the project "Cortical neuronal mechanisms of behavioural and cognitive deficits after sleep deprivation".

The first aim of this project is to investigate wake- and experience-dependent changes in cortical neuronal activity during sleep deprivation at the level of individual neurons, local neuronal assemblies and distributed cortical networks. The hypothesis will be tested that the changes in the firing patterns of cortical neurons during prolonged waking arise as a result of their preceding activity. The second aim of this project will be to investigate whether and how the changes in cortical neuronal activity during sleep deprivation lead to changes in sensory processing, behaviour and cognition. To this end, visual stimulation, sensory gating and ‘oddball’ paradigms, and spatial navigation and reaction time tasks will be used. These manipulations will be used on one hand to selectively engage and activate specific cortical areas and on the other hand to test the hypothesis that extensive use of specific cortical neurons and/or neuronal assemblies during waking would selectively and progressively depress their function, as would be expected after sleep deprivation.

The successful applicant should have a strong interest in neurosciences, and be highly motivated to perform experiments. Practical experience in in vivo electrophysiology, good quantitative and programming skills (Matlab) and knowledge in electrical engineering are important. Previous experiences with the visual system, in vitro work, pharmacology and focal viral delivery will be advantageous. Proficiency in the English language, good communication and social skills are important.

Please, send your applications to v.vyazovskiy@surrey.ac.uk