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Characterising the translatability of mice models of human ageing: a behavioural comparison of multiple memory functions in humans and mice


Department of Neuroscience, Psychology and Behaviour

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Dr Carlo De Lillo No more applications being accepted Competition Funded PhD Project (Students Worldwide)

About the Project

Mice are very promising models of human ageing as they are affected by similar decline associated to heathy ageing and diseases as observed in humans. Nonetheless, translating findings from mice models into successful interventions in people is still proving challenging (Gotz et al. 2018). Thus, it is important to characterise which functions decline in human in relation to heathy ageing and dementia and are appropriately modelled in mice. The assessment of memory functions in mice models is meaningful only when completed with tasks pertinent to the ethology of the species (Gerlai and Clayton, 1999). Equally critical is the ecological validity of memory tasks in studies of healthy aging and dementia in people (Bayley et al 2010; Burgess et al. 2006). This project entails testing mice with a naturalistic search/foraging task, recently developed by the supervisors. The task allows measuring several functions (Working-memory; Long-term-memory and monitoring patterns of reward availability, thus acting as a cognitive test-battery within a single task. An immersive Virtual Reality (VR) version of the task, also piloted by the supervisors, allows the comparison of people and mice. Search is a ubiquitous cognitive problem in humans (Hills et al., 2015), required by activities ranging from internal scanning of semantic memory to everyday real-world tasks (e.g. searching for missing keys). The project assays memory functions involved in search tasks in young/old participants and AD sufferers. It will reveal functions selectively affected by dementia in people, as well as whether or not they are adequately modelled by mice models. Pilot data show striking similarities between young adult humans and young mice in these functions. The present project features testing mice (young healthy, aged, AD models) and people (< 35 YOA; over 65 YOA, AD sufferers).
Objectives:
1. To determine which functions decline with age or AD and are appropriately modelled in mice.
2. To validate a new testing battery for mice and humans based on a single simple task.
3. To identify new indicators of early cognitive decline in dementia in people.
Methods:
The study is based on a newly developed task where mice (tested in an arena) and people (tested with a VR version of it) search for rewards (sugar pellets or food images) among sets of containers. An olfactory version will be used with AD mice models (Tg2576) prone to develop retinal disease. The structure of the task will be identical except that the containers to search will be scented with essential oils, rather than being differentiated by colour patterns. Independent variables are: species (humans/mice); presence/absence of disease (people with AD/controls, Tg2576/control mice; age (young/old). The dependent variables are behavioural measures of different memory functions assessed by the task.
Entry requirements:
• Those who have a 1st or a 2.1 undergraduate degree in a relevant field are eligible.
• Evidence of quantitative training is required. For example, AS or A level Maths, IB Standard or Higher Maths, or university level maths/statistics course.
• Those who have a 2.2 and an additional Masters degree in a relevant field may be eligible.
• Those who have a 2.2 and at least three years post-graduate experience in a relevant field may be eligible.
• Those with degrees abroad (perhaps as well as postgraduate experience) may be eligible if their qualifications are deemed equivalent to any of the above
• University English language requirementsapply. https://le.ac.uk/study/research-degrees/entry-reqs/eng-lang-reqs/ielts-65

For further information please contact [Email Address Removed]
Application advice:
To apply please refer the application instructions at https://le.ac.uk/study/research-degrees/funded-opportunities/bbsrc-mibtp

You will need to apply for the PhD place and also submit your online application notification to MIBTP. Links for both are on the above web page.

Project / Funding Enquiries: For further information please contact [Email Address Removed]

Application enquiries to [Email Address Removed]

Funding Notes

All MIBTP students will be provided with a 4 years studentship.
Tuition Fees at UK fee rates
- a tax free stipend of at least £15,295 p.a (to rise in line with UKRI recommendation)
- a travel allowance in year 1
- a travel / conference budget
- a generous consumables budget
- use of a laptop for the duration of the programme

References

1. Bailey, P.E., Henry, J.D., Rendell, P.G., Phillips, L.H. & Kliegel, M. (2010) “Dismantling the “age–prospective memory paradox: The classic laboratory paradigm simulated in a naturalistic setting” Quarterly Journal of Experimental Psychology, 63, p.646-652

2. Burgess, P. W., Alderman, N., Forbes, C., Costello, A., Laure, M. C., Dawson, D. R., … & Channon, S. (2006). The case for the development and use of “ecologically valid” measures of executive function in experimental and clinical neuropsychology. Journal of the International Neuropsychological Society, 12(02), 194–209.

3. Götz, J., Bodea, L. & Goedert, M. (2018). Rodent models for Alzheimer disease. Nature Review Neuroscience 19, 583–598.

4. Hills, T. Todd, P.M. Lazer, D. Redish, D. (2015) Exploration versus exploitation in space, mind, and society. Trends in Cognitive Sciences. 19 (1): 46-54.
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