| Čoahkkáigeassu: | <p>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.</p>
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