Separate lines of evidence have shown that age-related impairments in memory are correlated with the prenatal availability of choline and changes in rapid eye movement (REM) sleep. For example, prenatal choline supplementation leads to adult modifications in cholinergic metabolism that are associated with enhancements in cognition and reduced age-related decline in memory. In addition, evidence that deficits in both REM sleep and memory are ameliorated in adult animals by cholinergic agonists suggests that organizational changes in cholinergic metabolism may be able to alter the structure and continuity of sleep in adulthood and directly influence cognitive processes. In order to investigate the relationship between sleep and the prenatal availability of choline, baseline levels of REM and slow-wave sleep (SWS) will be measured as a function of prenatal choline deficiency, sufficiency, and supplementation in adult rats. The overall goals of the project are to conduct a series of studies that will determine if adult animals with variations in choline metabolism caused by the prenatal availability of choline have selective alterations in the quantity or quality of sleep that are evident early in adulthood and are sustained or enhanced with aging. The proposed studies will also examine whether changes in sleep patterns (e.g., ratio of SWS to REM sleep) are associated with age-related changes in behavior and whether different types of behavioral tasks (e.g., hippocampal or non-hippocampal dependent) are differentially sensitive to alterations in sleep patterns as a function of age and early choline availability. Ensemble recording techniques will be used in order to access the efficacy of hippocampal-neocortical reactivation mechanisms that may be involved in the consolidation of memory processes as a function of the prenatal availability of choline in 4 mo, 14 mo, and 24+ mo old rats. A final series of experiments is designed to develop a murine model of cholinergic metabolism as a function of apolipoprotein e-deficiency, prenatal choline availability, gene dosage, and age. All of these studies are designed to evaluate the relationships between sleep control mechanisms and the memory enhancing effects of prenatal choline supplementation in young, mature, and aged animals.
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