Proceedings of The Physiological Society

Sleep Sleep and Circadian Rhythms (London, UK) (2018) Proc Physiol Soc 42, C08

Poster Communications

Age, Alzheimers, circadian rhythms and sleep in Drosophila

E. Buhl1, J. Curran1, J. Higham1, J. Hodge1

1. Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol, United Kingdom.

All organisms on earth are subject to predictable daily environmental changes caused by the earth's rotation, therefore they have evolved circadian clocks that regulate changes in behaviour, i.e. activity and sleep, as well as in physiology and metabolism to ensure they occur at certain times allowing adaption to the environment. All studied animals, from jellyfish to humans, show some form of sleep and while it is still not resolved why we sleep, it is essential for life since sleep deprivation is detrimental to health and shortens lifespan. We use Drosophila to study this fundamental behaviour because flies offer numerous advantages for investigating sleep and the clock, not least the strong history of circadian research in the model organism, genetic tractability, short lifespan, rapid generation time as well as clearly defined and manipulatable neural circuits. Capitalising on fly genetics we are using both behavioural tests of circadian and sleep activity and electrophysiological recordings from the wake-promoting, pigment dispersing factor (PDF)-positive, large lateral ventral neurons (l-LNV). As in humans where it is well established that elderly individuals have increasing difficulties sleeping at night and have an increase in daytime sleep episodes, we show that sleep in aged flies is increased at day but not at night with significantly increasing sleep duration whilst reducing sleep latency. We demonstrate that the age-dependent decline in circadian output is combined with changes in the daily activity of Drosophila, namely a reduction in morning and evening anticipatory behaviour. Furthermore, the arousal specific l-LNVs change their electrical properties with age with a significant decrease in input resistance but no significant changes in spontaneous electrical activity or membrane potential. We also demonstrate a reduction in the daily plasticity of the synaptic architecture of the s-LNv neurons, likely to underlie the reduction in circadian rhythmicity during ageing. Alzheimer's Disease (AD) is the most common cause of dementia, and is associated with sleep and circadian rhythm defects. We show that driving expression of human 4R0N tau - that is associated with AD pathology - in the Drosophila clock gives rise to a phenotype which closely matches the behaviour seen in human AD patients. Tauopathic flies exhibited greater locomotor activity throughout the day and night and displayed a night-time-specific loss of sleep. Under constant darkness, the locomotor behaviour of tau-expressing flies was less rhythmic than controls indicating a defect in circadian rhythm. Current clamp recordings from l-LNVs revealed elevated spontaneous firing which likely underlies the observed phenotype. These results provide further insights into the effect of ageing and AD on circadian biology, demonstrating changes in electrical activity in conjunction with the decline in behavioural outputs.

Where applicable, experiments conform with Society ethical requirements