Grant: Discovery Grants Program - Individual

My research consists of five major projects, all of which involve the behavioural phenotyping of mice. The objectives of each project are as follows: (1) How reliable and valid are mouse models of neurodegenerative and other diseases? When a genetically modified mouse is developed as a model for Fragile X disorder, Alzheimer's Disease, ADHD or other human disorders, how can we determine their neuro-behavioural abnormalities? We will use our behavioural test battery to test proposed mouse models to determine which of their behaviours are normal, which are abnormal and how their behaviours change with age. (2) How do the sensory abilities of mice affect their cognitive performance? Many commonly used inbred strains of mice have age-related visual and/or auditory impairments. We will use our behavioural assays to dissociate sensory malfunction from cognitive deficits so that we can determine whether a mouse is cognitively impaired (an Alzheimer's model mouse) or has a sensory malfunction (a blind mouse). (3) What are the effects of apparatus design and test procedure on mouse behaviour? We will study how the design of test apparatus and procedures for studying mouse behaviour in the Barnes circular maze, the set-shifting paradigm, the 5-choice serial reaction time task, Hebb-Williams maze and 8-arm radial maze effects learning and memory strategies and anxiety-like behaviour in mice. (4) How do neural changes in transgenic mice correlate with behavioural changes? When we find a transgenic mouse with behavioural abnormalities, we will investigate the neural basis of these abnormalities by examining the brains histologically with immunospecific stains for changes in cell survival, cell death (apoptosis), axon and dendrite size, number of synapses and for neurochemical activity (ACh, AChE, DA, NE, 5-HT). (5) What is the error rate in mouse behavioural experiments and how can errors be detected, measured and reduced? ""Laboratory effects"" account for a high proportion of the variance in mouse behavioural studies. We will examine experimenter, mouse, procedural and apparatus variables which lead to different results when the same experiment is performed at different times in the same laboratory.