Sleep is well-established to become more superficial and fragmented as we age, with deficits in cognitive processing also commonly observed. While effects have been identified in both humans and mice (used in this thesis), there are important species differences in these findings and importantly, very little is known about the neural dynamics underlying these changes. By integrating several state-of-the-art approaches from putative single unit electrophysiological recordings to behavioural and pharmacological assessments, this thesis aimed to provide novel insights into the neural mechanisms involved in the age-dependent changes in sleep and cognition in mice. Firstly, this thesis investigated the neural activity underpinning the known global sleep changes that occur with ageing. Surprisingly, the majority of neuronal measures quantified in this study were resilient to the effects of ageing. Therefore the global sleep disruptions identified with ageing are unlikely to arise from changes in local cortical activity. Secondly, diazepam injection was found to suppress neural activity, in addition to previously reported effects on electroencephalography (EEG). Subtle differences in the effects of diazepam were identified across age groups, which may account for the variability seen in the efficacy of benzodiazepines in older individuals. Thirdly, ageing and sleep deprivation were found to have only a few effects on performance in a spatial learning task, the Morris water maze (MWM). Suggesting that spatial learning may be fairly resilient to the effects of ageing and sleep deprivation. Finally, this thesis presents preliminary analyses that showed mice were able to perform two novel paradigms of the visual discrimination task, suggesting their suitability in studying the link between ageing, sleep and cognition. Together the studies presented in this thesis provide insights into the differences between global and local mechanisms affected by ageing. Only by understanding local mechanisms will we be able improve on current treatments aimed at helping with the unwanted effects of healthy ageing, such as cognitive decline and sleep disruptions.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:757927 |
| Date | January 2018 |
| Creators | McKillop, Laura |
| Contributors | Vyazovskiy, Vladyslav V. ; Davies, Kay E. ; Wafford, Keith A. |
| Publisher | University of Oxford |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://ora.ox.ac.uk/objects/uuid:a3c762ab-cbc0-4095-86db-99e04dc7e84f |
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