Grant: Operating Grant - Priority Announcement: Aging (Bridge Funding)

Learning and memory require information exchange between brain cells in circuits that pair at least two different environmental inputs in space and time. For example, when we meet someone new, visual and auditory pathways are activated and this information is routed to the hippocampus, a brain region in which the convergent activity leads to storage of information. Memory is the ability of the brain to re-call established circuits so that the next time we see the person or hear his/her voice we remember his/her name. For reasons that remain elusive, these circuits are particularly vulnerable to dysfunction in Alzheimer's disease (AD) patients. Subtle changes in these circuits are responsible for the death of brain cells in regions of the brain where information is stored, one of which is the hippocampus. The death of populations of brain cells in AD patients apparently occurs over a prolonged time period of many years, this is why, slowly but surely, AD patients lose their memory and even their personalities. Due to advances in genetic engineered mice, we have generated a mouse line with a phenotype that are similar to some of the characteristics of AD patients. Indeed, we have initiated some experiments with these mice and we found that they behave like animals with memory deficits. I propose to study the hippocampus of these animals using a multidisciplinary approach in order to better understand the chemicals known to be related to memory impairment of AD patients. It is also hoped that the findings of our investigation will help to develop innovative treatments for AD patients.