WORM_SLEEP · Sleep homeostasis in Caenorhabditis elegans
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-06-01 → 2020-05-31
- EU contribution
- €166,157
- Participants
- 2
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Sleep homeostasis in Caenorhabditis elegans
Sleep is a ubiquitous phenomenon across the animal kingdom, and problems in sleep patterns are a major health concern both primarily and in combination with other pathologies. Despite the importance of sleep for human and animal health, sleep function is still an unsolved mystery in neuroscience. Main hypotheses, which have been suggested throughout the years, include energy allocation, memory consolidation, rescaling of synaptic strength, clearance. Evidences collected in various animal species support each of those, but what remains to be answered is whether any of these functions is more primary than the others, in evolutionary terms. The question is best addressed by studying sleep in a comparative way, across the highest possible number of animal species, and by investigating organisms with smaller and less architecturally complex brains. The nematode Caenorhabditis elegans with his compact 302 neuron-brain and resolved connectome offers a unique possibility of getting a deeper insight into this fascinating mystery. The goal of this project was to unravel the neural regulation of sleep in C. elegans and to establish a tool for sleep deprivation which would be useful to gain a better understanding of what the main function of sleep in this organism, and possibly across organisms, is. More in detail, the smaller-scale objectives were: characterizing a type of sleep where studying the effects of deprivation would be feasible without interfering with the survival of the animal, studying its genetic and neural bases, and finally investigating possible sleep deprivation approaches, in order to subsequently study the effect of sleep deprivation on brain dynamics.
Data: CORDIS, © European Union
Project objective
The aim of my research is to unravel one of the biggest unresolved problems in neuroscience: the function of sleep. Sleep is an essential aspect of our lives, the importance of which appears clear in pathological conditions where its normal patterns are disrupted. Moreover, it is an evolutionary conserved phenomenon. It has been described and characterized at levels, ranging from behavioural to neural and molecular, in different animal species. Despite its conservation, pointing to a fundamental function in animal survival, the reason for sleep is still debated. Different hypotheses have been raised, such as the energy hypothesis, the synaptic homeostasis hypothesis, and the clearance hypothesis; there is evidence to support each. However, no conclusive agreement on the main reason why sleep evolved has been reached. This is mainly due to the difficulty in integrating the above-mentioned levels of characterization in a single model organism. I will overcome this limitation by studying sleep homeostasis in the nematode Caenorhabditis elegans. Since sleep is a global process spanning the entire brain, full understanding of its regulations requires investigation at levels ranging from molecular mechanisms in single cells to brain-wide network activity. This is currently achievable only in C. elegans, providing a small anatomically mapped nervous system, advanced genetic tools, and a novel whole-brain imaging approach with single-cell resolution that was developed in my host lab. I will leverage on this approach, as well as a new quantitative behavioural paradigm for sleep homeostasis in adult worms, to study the brain-wide effects of sleep deprivation. To unravel the essential function of sleep, I aim to:I: Characterize adult C. elegans sleep by quantitative behavioural analysis and whole brain imaging.II: Identify the neural signature of sleep deprivation. III: Isolate the final signal communicating sleep propensity to sleep-promoting centres.
Original text from CORDIS.
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Data: CORDIS, © European Union