Rewarding experience and the aging brain

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DESCRIPTION (provided by candidate): Aging is associated with a decline in cognitive function that begins in midlife. Age-associated deficits in learning and memory are often accompanied by impaired synaptic and structural plasticity in the hippocampus, including diminished adult neurogenesis. Individual differences in the rate of cognitive decline with aging are probably due to the combined influence of genetic and environmental factors. Indeed, experience has been shown to alter both cognitive function and hippocampal plasticity in adulthood. Exposures to aversive experiences, such as shock, cold swim, and predator exposure, negatively affect hippocampal structure, at least in part by elevating stress hormones. Compared to those of a negative nature, positive experiences involve a rewarding or motivating component-examples including running, eating a high fat diet, and sexual behavior. Each of these experiences activates the HPA axis. Evidence suggests that sexual experience paradoxically increases both glucocorticoids and adult neurogenesis in the young adult hippocampus, but no studies have examined its effects on the aging brain. To investigate the influence of a rewarding social experience on the aging brain, the following specific aims will be addressed: 1) to determine whether sexual experience reverses age-associated changes in adult neurogenesis and 7 dendritic architecture, and 2) to determine whether sexual experience mitigates age-associated cognitive deficits. These specific aims will explore the interrelationships among rewarding experience, aging, hippocampal structure, and learning by comparing the effects of acute and chronic sexual experience on the following: adult neurogenesis, using BrdU labeling and immunofluorescence; dendritic spines, using Dil and Golgi staining; spatial navigation ability using the Morris water maze. These studies are designed to fill the gaps in our current knowledge and potentially lead to understanding the mechanisms underlying predisposition and resistance to age-induced deficits in neurogenesis and cognitive decline. PUBLIC HEALTH RELEVANCE: the mean life expectancy is extended due to advances in modern science and medicine, many concerns regarding the physical and mental well-being of the aged have been raised. Age- induced alterations in structural plasticity (i.e., neurogenesis, spine density) in the hippocampus may be involved in the functional abnormalities associated with cognitive decline, with experiences possibly ameliorating these effects. The studies outlined in this proposal are designed to fill the gaps in our knowledge surrounding these topics, with a view toward understanding the mechanisms underlying predisposition and resistance to age-induced deficits in structural plasticity and cognitive decline.