1 Place Cell Physiology in a Transgenic Mouse Model of Alzheimer’s Disease

I, Ming YI, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by progressive cognitive impairments (Selkoe, 2001). Hippocampal place cells are a well understood candidate for the neural basis of one type of memory in rodents; these cells identify the animal's location in an environment and are crucial for spatial memory and navigation. This PhD project aims to clarify the mechanisms responsible for the cognitive deficits in AD at the hippocampal network level, by examining place cell physiology in a transgenic mouse model of AD. I have recorded place cells in tg2576 mice, and found that aged (16 months) but not young (3 months) transgenic mice show degraded neuronal representations of the environment. The level of place cell degradation correlates with the animals ' (poorer) spatial memory as tested in a forced-choice spatial alternation T-maze task and with hippocampal, but not neocortical, amyloid plaque burden. Additionally, pilo