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Séminaire - Richard Brown Age-related changes in learning and memory among multiple memory systems in mouse models of Alzheimer's disease.

Abstract :

Richard Brown de Dalhousie University (Halifax, NS, Canada)


  We examined age-related changes in spatial learning and memory, procedural learning and memory, and olfactory memory in male and female APP/PSEN1 double transgenic, 3x-Tg AD and 5XFAD mouse models of AD and their appropriate control strains between 3 and 18 months of age.  The 5xFAD mouse has the APP transgene with the Swedish (K670N/M671L), Florida (1716V) and London (V7171) mutations and a presenilin transgene with M146L and L286V mutations.  

The controls are wild-type litter mates.  The 3xTg-AD mouse has the human amyloid precursor protein (APPswe),  a mutated mouse presenilin-1 (PS1M1461), and a transgene associated with tau pathology (Tau301L).  The B6129S1F2 mice are used as controls.  The APP+PS1dE9 mouse has APP with a Swedish mutation (K670N/M671L) and mutant human presenilin (dE9) and has the B6C3F1/J mice as controls.  
The data presented examines the concept of multiple memory systems and their changes with age, the neuropathology of each mouse strain and the relationship of this neuropathology with the age-related decrements in visuo-spatial, motor and olfactory learning and memory.  The data examines genotype, age, and sex differences on each memory system to examine the effects of the transgenes on different memory systems.
 There were no genotype or age-related deficits in olfactory memory.  The 5xFAD mice had age-related deficits in procedural learning. There were also age-and genotype-related deficits in visuo-spatial memory.  Confounding effects of background strain, behavioural measures and housing conditions will be discussed.

Selected publications

•O’Leary, T.P. and  Brown, R.E.  Optimization of apparatus design and behavioural measures for the assessment of visuo-spatial learning and memory of mice on the Barnes maze.  Learning and Memory, 2013, 20, 85-96.
• O'Leary, T.P. , Gunn, R.K.,  and Brown, R.E.  What are we measuring when we test strain differences in anxiety in mice?  Behavior Genetics,  2013, 43, 34-50.  
• Wong, A.A. and  Brown, R.E.   A neuro-behavioral analysis of the prevention of visual impairment in the DBA/2J mouse model of glaucoma.  Investigative Opthalmology and Visual Science (IOVS), 2012, 53 (9), 5956-5966.
• Brown, R. E.   Improving animal models for nervous system disorders.   Genes Brain and Behavior, 2012, 11, 753-756.
• Schellinck, H. M., Cyr. D.P. and Brown, R.E. How many ways can mouse behavioral experiments go wrong?  Confounding variables in mouse models of neurodegenerative diseases and how to control them. Advances in the Study of Behavior, 210,  41, 255-366.

Scientific focus :

Research in my laboratory looks at different aspects of rodent behaviour. We are developing a set of standardized test batteries to study the behaviour of inbred, mutant and knockout mice. This includes an "ethological" test battery, a learning and memory test battery and a developmental test battery. Tests used include visual acuity, rotarod, elevated plus maze, elevated zero maze, open field, light-dark box, Hebb-Williams maze, Barnes maze, water maze, olfactory discrimination learning, olfactometer, cued and context conditioning, nine hole box, and others. We use these tests to study roden