Considerations in behavioural phenotyping of genetic mouse models of Alzheimer’s disease and frontotemporal dementia

Organizer: Szu-Han Wang, University of Edinburgh, UK

Description:
In this symposium, we will report our first-hand observation of behavioural measurements in the assessments of cognitive functions in a few examples of genetic mouse models that are commonly used to capture key pathologies of Alzheimer’s disease and frontotemporal dementia. We will draw comparison of our findings with other published studies. We will summarise the consistent changes in memory, emotion, motor, and sensory phonotypes across labs. Critically, we will elucidate the difference in behavioural apparatus, testing procedures, measurements, animal histories, and environmental factors that contribute to the discrepancies in findings and to the challenges in translational implication. A panel discussion will be arranged to conclude the session.  

Schedule (speaker names will be added after their abstracts have been reviewed and accepted:

• Behavioural, cognitive and sensory phenotyping of knock-in mouse models of Alzheimer’s disease and frontotemporal dementia.
  We have undertaken longitudinal phenotyping studies of the App^NL-F/NL-F and App^{NL-G-F/NL-G-F} mouse models of amyloid accumulation and Tardbp^Q331K/Q331K and C9orf72^GR400/+ mouse models of frontotemporal dementia (FTD). This includes touch screen tasks, assessing visual-discrimination-reversal and paired-associate learning. Also, home cage analysis of behaviour, the three-chamber test of social motivation and Sanderson forced Y-maze test of short-term memory. We have also tested olfaction and visual function (optokinetic drum test) to understand if sensory confounds affect test performance in these commonly used animal models.
• Behavioural characterisation of APP-KI mice
  Rodents’ innate exploratory behaviour serves as an invaluable platform for studying cognitive processes, without externally imposed rules or reinforcement. This presentation will summarise our research findings, primarily focusing on the Novel Object Recognition and Object Location tasks and will draw comparisons with similar studies utilizing the same mouse models. In addition, we address crucial considerations essential when designing and conducting such experiments. Our work underscores the significance of utilizing rodent exploratory behaviour paradigms to advance our understanding of memory processes and cognitive function.
•  The influence of behavioural measurement and history in memory phenotypes
  of APP-KI mice.
  Dry-land mazes are commonly used to characterise memory phenotypes
  in genetic mouse models of Alzheimer’s disease. Using a relatively simple
  apparatus such as a Y-maze, mixed results of spontaneous alternation in the Y-maze, as a proxy of working memory, are reported using an APP-KI model of Alzheimer’s disease. In this talk, we will compare across studies to describe differences in behavioural measurement and history that likely contribute to mixed results, to introduce a novel dry-land maze task, and to inform future phenotyping studies.
• Cognitive and behavioural phenotyping of APP-KI mice in the home cage enclosures
  In this talk, I will describe spatial memory and other behaviours of APP-KI mice automatically assessed in home cages such as smart-Kages and Intellicages. I will also compare the results with performance measured in analogous standard tests.