Grant: Master's Award: Canada Graduate Scholarships

Tau neurofibrillary tangles are one of the hallmarks of Alzheimer's Disease. Evidence suggests that different neurons throughout the brain are affected differently by tauopathy so we would like to observe the effects of pre-tangle tau on various brain areas and their associated behavioural functions. To do so, we will use an animal model where Sprague Dawley rats will be infused with a pretangle pseudophosphorylated human tau (htauE14) and these animals will then receive an infusion of AAVdj-PRSx8-htauE14- EGFP in the LC or AAVdj-CaMKII-htauE14-EGFP in the PC or hippocampus. We hypothesize that htauE14 will alter neuronal excitability over time and these deficits will correlate with behavioural data. In order to test this hypothesis, animals will undergo olfactory behavioural tests including a go/no-go odor discrimination task and spatial behavioural tests such as the spontaneous spatial pattern discrimination task. Behavioural deficits are expected to be specific to the site of infusion. In parallel with these behavioural experiments, we will also conduct in vitro electrophysiology at various time points post-infusion. Synaptic deficits are likely the primary signs of neurodegeneration caused by htauE14 so we expect to see decreased excitability and synaptic properties in htauE14 animals prior to the onset of behavioural deficits. Observing more than one brain area will allow us to understand the rate of tauopathy progression and correlated behavioural and electrophysiological deficits specific to those areas. These experiments in parallel will allow us to better understand pretangle stages that occur prior to the onset of clinical symptoms and the knowledge gained from this study could lead to the development of effective AD treatment strategies.