The ability to remember and use information accurately is very important, and impairments of timing and temporal memory profoundly disrupt an individual's life. These observations motivate research to understand the brain mechanisms involved in normal memory processing, and the types of pathology that produce timing dysfunctions and amnesia. Previous work in rats, monkeys, and humans has demonstrated that lesions of frontal and temporal lobe structures, particularly the hippocampus and frontal cortex, produce behavioral changes that have some of the basic characteristics of an amnesic syndrome. The purpose of the present proposal is to apply a quantitative information processing model of timing behavior to data obtained in rats showing individual differences in the content of temporal memory. The nature of these individual differences in the content of temporal memory will be evaluated by examining a number of selected variables. The contribution of external influences, such as stimulus modality and stimulus intensity, on the content of temporal memory will be investigated in the first experimental module. In the second and third experimental modules, physiological activity of cholinergic neurons as measured by choline uptake in the hippocampus and frontal cortex and patterns of electrical activity as measured by theta rhythm in these same areas will be examined as possible indices of the magnitude and direction of temporal memory dysfunction. The fourth experimental module investigates the developmental contribution to alterations in the content of temporal memory. Here the effects of pre- and postnatal choline supplementation on the short-term facilitation of memory and the long-term protection against age-related changes in memory are evaluated. Together, these experiments help to determine the extent to which rats can be used as a model to investigate the brain mechanisms involved in timing and temporal memory dysfunctions that can be applied to other mammalian species.
