We all know that ageing can affect our memory, particularly our ability to discriminate between similar events. For example, our ability to remember ‘where I put my car keys today’ as opposed to ‘where I put them yesterday’ becomes increasingly difficult as we get older. Pattern separation refers to the process of representing highly similar memories in distinct ways so they can coexist without interference; it is one of the first memory processes affected by ageing.
Pattern separation is a function of the hippocampal dentate gyrus that comprises granule cells, mossy cells, and different classes of interneurons. Mossy cells, in particular, are essential to pattern separation and are key regulators of circuit dynamics in the dentate gyrus because they influence the balance between excitation and inhibition at different frequencies. Because each class of interneuron has very different intrinsic firing propeties, our theory is that mossy cells inhibit granule cells across a range of frequencies by recruiting different interneuron classes at different frequencies. This project will involve recording and manipulating the dynamic responses of mossy cells, granule cells and different classes of interneurons in the dentate gyrus using optogenetics and in vitro electrophysiology. We also plan to manipulate the activity of these cell populations using optogenetics during behavioural memory tasks. The results of these experiments will then be used to develop a computational biophysical model of DG circuitry and pattern separation. The model will include the intrinsic properties of known cell types of the dentate gyrus, their ion channels, receptors, and dendritic morphologies to recapitulate the spatiotemporal dynamics of the circuitry as closely as possible. Simulations will be implemented in Python or Julia and run on the University of Bristol's Blue Crystal supercomputer. The model will then be used to predict the effect of different pharmacological agents that target specific cell types, ion channels or receptors in the dentate gyrus. These predictions will be tested experimentally, as above, to prove the model.
The results from this project will advance our understanding of pattern separation and could well lead to novel strategies and drug therapies to tackle the decline of pattern separation and memory that can occur with age.
Our aim as the SWBio DTP is to support students from a range of backgrounds and circumstances. Where needed, we will work with you to take into consideration reasonable project adaptations (for example to support caring responsibilities, disabilities, other significant personal circumstances) as well as flexible working and part‐time study requests, to enable greater access to a PhD. All our supervisors support us with this aim, so please feel comfortable in discussing further with the listed PhD project supervisor to see what is feasible.
University of Bristol, Bristol Medical School:
Bristol Medical School is the largest and one of the most diverse Schools in the University of Bristol, with approximately 1100 members of staff, 1350 undergraduate, 250 postgraduate taught and 240 postgraduate doctoral research students. The Head of School is Professor Ashley Blom. The Medical School has two departments: Population Health Sciences and Translational Health Sciences. The School is a leading centre for research and teaching across these areas. Research in the School is collaborative and multi-disciplinary, with staff coming from a wide range of academic disciplines and clinical specialties.
The 2021 Research Excellence Framework (REF) confirmed the University of Bristol’s position as a leading centre for health research. Bristol Medical School contributed to three Units of Assessment including UoA1 (Clinical Medicine), UoA2 (Public Health, Health Services and Primary Care) and UoA4 (Psychology, Psychiatry and Neuroscience). The UoA2 submission, comprising predominantly Medical School staff. was ranked 3rd in the UK with 94% of our submitted research outputs rated as world leading (4*) or internationally excellent (3*). Submissions to UoA1 and UoA4 were shared with varying degrees of representation with the Faculty of Life Sciences. Respectively UoA1 and UoA4 had 94% and 84% of submitted research ranked as 4* or 3*, which represented increases in each category in the proportions of 4* ranked papers as well in growth in GPA rankings above the previous REF2014.
How to apply:
Apply here. Search for South West Biosciences Doctoral Training Partnership (PhD) under 'find a programme' Full details on how to apply for this project can be found here.
Funding includes a tax free stipend at UKRI rates (currently £17,668 for 22/23), research and training costs and tuition fees. Funding is also available for a limited number of international students.
Closing date:
Midnight, Monday 5th December 2022
Continue with Facebook
