EXAMINING OLFACTORY LEARNING AND MEMORY IN THE TRIPLE TRANSGENIC AND FIVE TIMES MOUSE MODELS OF ALZHEIMER'S DISEASE USING AN OPERANT OLFACTOMETER

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that is the leading cause of dementia. Olfactory dysfunction is one of the earliest symptoms of AD, and mice show a remarkable ability to learn olfactory based tasks. This thesis presents three studies that used transgenic mouse models of AD and assessed their performance in operant olfactometers. The first study examined the 3xTg-AD and 5xFAD models of AD on an olfactory detection task at six months of age. The female 3xTg-AD mice showed a decreased ability to detect ethyl acetate at the lowest concentrations presented compared to their wildtype controls, while there was no such deficit found in the male 3xTg-AD mice, nor the 5xFAD mice. The second study examined the 5xFAD model at 12 months of age on an odour detection task, and applied signal detection measures. Odour detection was not impaired in the 5xFAD mice, but learning was, and this learning impairment was worse in the female 5xFAD mice than the males. Female mice also showed a more conservative response bias. The third study assessed 5xFAD mice on an olfactory matching to sample working memory task at six months of age. This was the first study to demonstrate that mice could perform such a task, with all mice able to learn the task with a two second delay, and the best performing mice completing delays up to 30 seconds. The 5xFAD mice showed no working memory deficits on this task, though the female mice performed better than the males. Taken together, these studies highlight the remarkable abilities of mice to perform olfactory based tasks and demonstrate their use in assessing mouse models of AD.