- Vacancy Reference Number
- 2020CCBSPHD
- Closing Date
- 29 Feb 2020
- Salary
- 15000
- Address
- Centre for Clinical Brain Sciences, University of Edinburgh
- Duration
- 3 years
PhD project: Understanding cellular and network mechanisms underlying memory dysfunction in Alzheimer’s disease.
Summary: 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.
Reference: Fernández E, Collins MO, ..., Komiyama NH, Grant SGN. (2017). Arc Requires PSD95 for A Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence. Cell Rep. 21:67. Finnie P, Gamache K, ..., Wang SH*, Nader K. (2018). Cortico-hippocampal schemas enable independent fear conditioning in rats. Current Biology, 28:2900-9. Roy DS, Arons A, ..., Ryan TJ, Tonegawa S. (2016). Memory retrieval by activating engram of early Alzheimer’s disease. Nature, 531, 508–12. Wang SH*. (2018). Novelty enhances memory persistence and remediates propranolol-induced reconsolidation. Neuropharmacology 41:42-54.
Further Information
BSc or MSc in Biomedical Sciences, Neuroscience, Pharmacology, Psychology or related disciplines. Essential skills: rodent behaviour, immunohistochemistry, fluorescent microscopy
Desirable skills: stereotaxic surgery.
Contact Details
Apply via the EdNeuro.PhD gateway with a deadline on 29/02/2020 and interview in March 2020. For further enquiry, please contact s.wang@ed.ac.uk
