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Understanding cellular and network mechanisms underlying memory dysfunction in Alzheimer’s disease


College of Medicine and Veterinary Medicine

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Dr S Wang , Prof S Grant No more applications being accepted Funded PhD Project (European/UK Students Only)

About the Project

Memory impairment is among the early signs in Alzheimer’s disease (AD) that significantly affects daily function. It is vital to understand how neurons encoding memory (i.e. memory engram cells) are affected in the disease progression.

To visualise the engram cells, knock-in mice with venus-tagged activity regulated cytoskeleton associated protein (Arc) will be trained with memory tasks to provide a brain map of the memory circuit. To investigate how memory engrams are affect by AD, knock-in mice with amyloid precursor protein will be crossed with the Arc-venus mice. The spatial relationship between memory engram cells and AD pathology will be characterised. Finally, to substantiate the causal link between the engram cells and memory function, optogenetics will be used to rapidly and transiently stimulate the selective cell population for observing the recovery of memory function and the connection among engram cells across brain regions in the AD mice.

Together, this project will provide insights on the cellular and circuit mechanisms underlying memory loss in AD.

The recommended background of applicants to this project is: Behaviour, Cognition, Neurodegeneration or Psychology.
Essential skills are rodent behaviour, immunohistochemistry and fluorescent microscopy. Desirable skills are stereotaxic surgery.

Funding Notes

The deadline is 21st June 2020 and the interviews will be in early July. The studentship will start in January 2021. The funding will cover stipend, tuition fees at UK/EU rate, consumables and travel costs to attend an annual conference.

Previous applicants need not apply.

References

Fernández E, Collins MO, Frank RAW, Zhu F, Kopanitsa MV, Nithianantharajah J, Lemprière SA, Fricker D, Elsegood KA, McLaughlin CL, Croning MDR, Mclean C, Armstrong JD, Hill WD, Deary IJ, Cencelli G, Bagni C, Fromer M, Purcell SM, Pocklington AJ, Choudhary JS, Komiyama NH, Grant SGN. (2017). Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence. Cell Rep. 21(3):679-691.

Finnie P, Gamache K, Protopoulos M, Sinclair E, Baker A, Wang SH*, Nader K. (2018). Cortico-hippocampal schemas enable NMDAR-independent fear conditioning in rats. Current Biology, 28:2900-2909.

Roy DS, Arons A, Mitchell TI, Pignatelli M, Ryan TJ, Tonegawa S. (2016). Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease. Nature, 531(7595), 508–512.

Wang SH*. (2018). Novelty enhances memory persistence and remediates propranolol-induced deficit via reconsolidation. Neuropharmacology 41:42-54.


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