A disturbance of recent memory or the retention of newly acquired information is one of the fundamental features of aging. The central goal of the proposed experiments is the further delineation of the types of memory that decline with age and the understanding of the mechanism of such decline at the synaptic level of analysis. An animal model of age-related memory dysfunction has been identified in the Fischer 344 rat. Two-thirds of aged members of this species develop an impairment in spatial memory having characteristics similar to human amnesias. As in the human amnesias, the rodent memory loss is associated with disturbance of function in the hippocampal formation. The proposed research employs behavioral, electrophysiological and quantitative electron microscopic techniques to examine the neurobiological basis of the age-related memory deficit. Using a circuit analysis approach, the experiments are designed to examine age- related alterations in synaptic connectivity in the tri-synaptic hippocampal circuit as well as in a non-hippocampal cortical area as a control. Changes in synaptic connectivity could alter the flow of information through the hippocampal formation and result in memory dysfunction. The individual differences in memory function observed among aged Fischer 344 rats provides an excellent model for investigating the synaptic substrates of normal memory function, as well as its decline. A related purpose of the research is to investigate, at the synaptic level, why newly acquired information is lost rapidly with age.
