Ageing and the Drosophila circadian clock

• Main Author: Curran, Jack
• Other Authors: Hodge, James
• Published: University of Bristol 2019
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767986

It is well established that elderly individuals have increased difficulty sleeping at night combined with falling asleep and waking up earlier. Although these age-related declines in circadian output are clearly observable in activity recordings of laboratory animals, the underlying changes in molecular and neuronal activity remain unknown. The fruit fly, Drosophila melanogaster, has long been used as a model for studying the circadian system and for ageing research. In this thesis Drosophila was used as a model to study the effect of ageing on circadian and sleep behaviour. Circadian behaviour was measured using the Drosophila Activity Monitoring system, recording activity of flies at various stages of the ageing process, demonstrating a linear decline in rhythm strength with age combined with an increase in period length. Weakened circadian output is combined with significant alterations of diurnal behaviour of Drosophila, namely a reduction in morning and evening anticipatory behaviour. Ageing also has a significant impact on sleep behaviour, significantly increasing sleep duration whilst reducing latency, with larger effects observed on day- time sleep. Age-related changes in neuronal activity were investigated using whole-cell patch clamp electrophysiology to record from large lateral ventral (l-LNV) clock neurons, finding that ageing was associated with a significant decrease in input resistance, but no significant changes in spontaneous electrical activity or membrane potential. Manipulating the electrical properties of the circadian system by knocking down expression of candidate ion channels in all clock neurons had significant effects on behaviour, linking electrical activity with clock outputs. The results presented in this thesis demonstrate the suitability of Drosophila as a model to interrogate how ageing effects the circadian clock, identifying Alterations in the electrical properties of the l-LNV neurons may underlie observed changes in diurnal activity and sleep, while decreased remodelling of the s-LNV neurons can explain weakened circadian behaviour.