Grant: Operating Grant

Canada is going to face a growing crisis of seniors living with a decline in cognitive faculties, such as attention, learning, and memory, as a common consequence of normal aging. Understanding the biological and cognitive changes during aging is critical to improving our elders' quality of life. This proposal will focus on the role of the cholinergic basal forebrain (BF) in the cognitive impairments associated with normal aging. The BF region of the brain is poised to play an important role in how the brain takes in information because it is the major source of the chemical acetylcholine (ACh) for brain areas critical to cognition. Extensive loss in this chemical's function and pathology at its source are prominent in Alzheimer's disease (AD); thus, they are hypothesized to contribute to the cognitive decline associated with normal aging. The proposed studies will examine how this region and chemical affect how the aging brain 'binds' information. Although the human cognitive literature has yielded substantial insights into the attention-dependent nature and broad brain systems involved in feature binding, the chemistry and specific downstream correlates of feature binding remain unknown. The proposed studies will (1) selectively remove ACh cells in brain regions important to feature binding in rats to establish an animal model of cholinergic BF dysfunction, (2) test aged rats, and (3) collect behavioural and functional neuroimaging data in normally-aging humans to test the validity of this rat model to normal aging across the lifespan in humans. Thus allowing us to compare the behaviour and brain regions of rats and humans while performing the same feature binding task. Success of these studies may provide an understanding of the mechanisms by which the cholinergic BF system contributes to normal cognition and cognitive deficits associated with cholinergic deficiency that have significant societal consequence, such as normal aging and pathological aging, like AD.