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Title: Exploring interactions between the sleep homeostatic process and cortical neuronal dynamics
Author: Thomas, Christopher William
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2020
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The need for sleep increases during wakefulness and decreases during sleep. This process, termed Process S, homeostatically regulates vigilance states, ensuring that individuals obtain a relatively constant daily quantity of sleep. Process S is thought to reflect the regulation of core functional properties of neurones, but many fundamental questions remain. In this thesis, a combination of electrophysiological, pharmacological and mathematical techniques are applied to better characterise interactions between the sleep homeostatic process and cortical neuronal dynamics. The local and activity-dependent origin of Process S was explored through novel computational models, demonstrating that variability in local neuronal firing rates in mouse motor cortex can predict the dynamics Process S measured both in the slow oscillation and also in population off periods. It was concluded that Process S at the local level reflects an integration of cortical activity over time, and at the global level reflects an integration over space. Multi-scale statistical properties of neuronal dynamics were then explored across the sleep-wake cycle, using the theory of criticality. It was found that neuronal avalanches indicative of criticality did not change as a function of Process S during wake, however, did so across vigilance states in association with slow wave activity. The results demonstrate one way in which the control of global brain dynamics might be intrinsically interlinked with the regulation of arousal and sleep. Neuronal dynamics in the waking brain state were then perturbed in mice using the serotonergic psychedelic, psilocin. Although the drug briefly disturbed sleep, no enduring changes were observed in sleep-wake architecture or in the dynamics of Process S, despite perturbation to ongoing neuronal dynamics. Finally, it is argued that these results support the possibility that sleep homeostasis does not serve the active homeostatic regulation of any one specific neuronal variable, but that Process S fundamentally corresponds to an intrinsic time-keeping mechanism, precisely tracking the passage of time in each state and thereby enabling only that a daily sleep quota is obtained. This perspective reconciles the global level of sleep need's dissipation from the local level of its accumulation and offers new insights into understanding both why each individual sleeps every day and why sleep duration shows dramatic differences across the animal kingdom.
Supervisor: Vyazovskiy, Vladyslav Sponsor: Biotechnology and Biological Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Neuroscience