Yi, M.; (2009) Place cell physiology in a transgenic mouse model of Alzheimer's disease. Doctoral thesis , UCL (University College London).

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Abstract

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, pilot data show that physiological changes of the hippocampus in tg2576 mice seem to start as early as 3 months, when no pathological and behavioural deficits are present. However, these changes are not obvious at the neuronal level, but only at the hippocampal network level, which represent hippocampal responses to environmental changes. Place cell recording provides a sensitive assay for measuring the amount and rate of functional deterioration in animal models of dementia as well as providing a quantifiable physiological indication of the beneficial effects of potential therapies.

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