Cerebellar substrates of age-related learning deficits

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DESCRIPTION (provided by applicant): With aged individuals comprising an increasing proportion of the world?s population, care and treatment of age-related disorders is of utmost importance. In the United States alone, the percentage of the population over 65 rose to 12 percent in the 1990s and will grow to 16 percent with the aging of the "baby-boomer" generation. The process of aging has many deleterious effects on both physical and mental functioning, including a decline or slowing in cognitive function. This cognitive decline is a usual consequence of both nominal and abnormal (e.g, Alzheimer?s disease) aging and typically manifests itself in the domain of learning and memory. The use of animal models has become an invaluable tool in our search to understand the biological substrates of learning and the deleterious effects of aging. Classical conditioning of the rabbit?s nictitating membrane (NM)/eyeblink response is an ideal paradigm in which to study aging. Age-related deficits have been reported for this task, but the underlying changes in the neural substrates have thus far been under investigated. The current proposal will examine age-related functional changes in cerebellar circuitry that is critically involved in this task. With the use of elecirophysiological techniques in in vitro slices, we hope to document differences in cellular excitability and synaptic plasticity between young and aging brain. These differences could help explain the age-related disruption of learning and ultimately lead to the development of therapeutic strategies.