This grant requests 1 year of funding support as a supplement to the Washington National Primate Research Center at the University of Washington. The goal of work in the parent grant is to provide support for a broad-based research and resources program, providing biomedical scientists the opportunity to conduct research using nonhuman primate (NHP) models for human health-related and NHP biologic issues. This goal will be attained through support for scientific intellectual resources, administration, animal support resources, facilities, and operations. The specific goal of this supplement proposal is to extend our pilot study, initially funded through a supplement awarded last year, of behavioral and neurophysiological changes that accompany aging in rhesus macaque monkeys. As an outcome of this work, we expect to gather new preliminary data in support of establishing a new research program for cognitive assessment and neurophysiological recordings in aged monkeys. Monkeys provide a strong model for advancing our understanding of the neurobiology of human memory and executive function due to robust cross-species similarities in the anatomy and connectivity of the medial temporal lobe and prefrontal cortex. However, there has been very little research on age-related changes in cognition and neural activity in monkeys. It has recently been demonstrated that rhesus macaques are the first non-hominid species to exhibit tau neurofibrillary tangles, and these tangles follow a progression similar to that seen in human Alzheimer?s Disease (AD). These findings suggest that further characterization of neural changes with aging in the monkey is likely to yield insights with high translational significance.
In Aim 1, we will add 2 additional aged monkeys to our cohort and identify the pattern of cognitive deficits in aged monkeys, using a battery of cognitive tasks.
In Aim 2, we will record from isolated single neurons across the full anterior-posterior extent of the hippocampus from one aged and two young monkeys engaged in a task of cognitive flexibility, a monkey version of the Wisconsin Card Sorting task. Interleaved with periods of task performance will be periods of rest, which will allow us to examine how resting state activity changes as a function of age and in relation to task performance. Our lab has extensive expertise in recording from the hippocampus of monkeys engaged in cognitive tasks, and we propose to extend this work to investigate the neurobiology of aging.
Loss of proper memory function both as a result of Alzheimer?s dementia (AD) and of normal aging is a chief complaint among the elderly. Due to robust cross-species anatomical similarities, monkeys provide a strong model for changes in cognition in human aging. This goal of this application is to conduct a pilot study of cognitive assessment and neurophysiological recordings in aged rhesus macaque monkeys, with the goal of increasing our understanding of the neurobiology of age-related cognitive decline.
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