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Effects of fasting-induced torpor on sleep and behaviour in mice


Project Description

This project will investigate the effects of food restriction on torpor in mice, the effects of torpor on subsequent behavioural performance and sleep, and will develop a standardized approach to detect the occurrence of torpor during food restriction. Food restriction, fasting or scheduled feeding in mice are routinely used in many laboratories worldwide in the context of behavioural neuroscience, studies on metabolism and circadian neurobiology. Laboratory mice are a facultative heterothermic species that readily display torpor bouts in response to food deprivation at the temperature levels commonly used in animal facilities. While torpor itself is an adaptive response to limited food supply, and is easily reversible, little is known about the lasting consequences of torpor on physiology, sleep and brain function, and thus it may be a potential source of significant biological variation in scientific data. The overarching aim of this project is to characterise fasting-induced torpor and its effects on sleep, behaviour and brain activity in mice.

The specific objectives of this project:

1. To investigate the likelihood of torpor initiation in commonly used fasting protocols in C57BL/6 mice, such as scheduled feeding used in circadian studies, maintenance of mice on 85% of freely-feeding body weight as used in behavioural studies and overnight fasting as used for glucose tolerance testing.

2. To characterise behavioural performance of animals after torpor. To this end, we shall investigate spontaneous behaviours, use the rotarod task, open field test and novel object recognition task.

3. To define the dynamics of sleep and brain activity which surround a bout of torpor in mice. We will perform electroencephalogram (EEG) recordings during torpor entry, maintenance and arousal out of torpor.

4. To develop the methodology for detecting torpor in food restricted mice. We will use a non-invasive approach, where peripheral body temperature will be monitored in mice undergoing food restriction paradigms.

The project will be co-supervised by Professors Vladyslav Vyazovskiy, Stuart Peirson and David Bannerman (University of Oxford) in collaboration with Dr Sara Wells (MRC Harwell). The project will commence in October 2019 within the Department of Physiology, Anatomy and Genetics at the University of Oxford.

Funding Notes

Applicants should hold or be about to achieve a First or Upper-Second (2.i) class degree in a relevant subject. NC3Rs Studentships are available to UK nationals and EU students who meet the UK residency requirements. Further information about eligibility can be found on the NC3Rs studentships website: View Website. This studentship will be considered on either a full-time or part-time basis. Application details View Website

Funding is available for 3 years with a minimum stipend of £14,777 per annum. Informal enquiries may be made to Professor Vladyslav Vyazovskiy at

Interview dates are scheduled for the end of March 2019

References

1. Jensen, T. L., Kiersgaard, M. K., Sørensen, D. B., and Mikkelsen, L. F. (2013) Fasting of mice: a review. Lab Anim 47, 225-240
2. Hudson, J. W., and Scott, I. M. (1979) Daily torpor in the laboratory mouse, Mus Musculus var. albino. Physilogical Zoology 52, 205-218
3. Gavrilova, O., Leon, L. R., Marcus-Samuels, B., Mason, M. M., Castle, A. L., Refetoff, S., Vinson, C., and Reitman, M. L. (1999) Torpor in mice is induced by both leptin-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 96, 14623-14628
4. Swoap, S. J., Gutilla, M. J., Liles, L. C., Smith, R. O., and Weinshenker, D. (2006) The full expression of fasting-induced torpor requires beta 3-adrenergic receptor signaling. J Neurosci 26, 241-245
5. Schubert, K. A., Boerema, A. S., Vaanholt, L. M., de Boer, S. F., Strijkstra, A. M., and Daan, S. (2010) Daily torpor in mice: high foraging costs trigger energy-saving hypothermia. Biol Lett 6, 132-135
6. Bouma, H. R., WVerhaag, E. M., Otis, J. P., Heldmaier, G., Swoap, S. J., Strijkstra, A. M., Henning, R. H., and Carey, H. V. (2012) Induction of torpor: mimicking natural metabolic suppresion for biomedical applications. J Cell Physiol 227, 1285-1290
7. Vyazovskiy, V. V., Palchykova, S., Achermann, P., Tobler, I., and Deboer, T. (2017) Different Effects of Sleep Deprivation and Torpor on EEG Slow-Wave Characteristics in Djungarian Hamsters. Cereb Cortex 7, 1-12


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FTE Category A staff submitted: 223.80

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