Impairment of memory is one of the most common and most perplexing signs of aging. The goal of this research project is to gain an understanding of the nature of how these memory deficits occur with advancing age. Drs. Morrell and deToledo Morrell are using an animal model of aging--a strain of rat which has a specific and identifiable memory impairment which occurs as the animal approaches the end of its expected lifetime: These animals show progressive performance deficits in their ability to learn spatial cues as they age. One of the most promising areas of research regarding the location in which memories are formed is the hippocampal formation, a region of the limbic forebrain which has been shown to be involved both in human and in animal memory functions. The nature of this memory deficit is being extensively characterized by the use of both spatial and non-spatial tasks (spatial tasks appear to be dependent upon a functional hippocampal formation, whereas non-spatial tasks are not). This specific deficit is measured by performance in a radial arm maze, a spatial task. An interdisciplinary team of investigators is exploring three major correlates of this memory deficit, by examining changes in: 1) synaptic morphology (the locus of connections between nerve cells). Modification of synaptic circuitry is examined in several sub-fields within the hippocampal formation by using new stereological methods of electron microscopy. 2) long term potentiation an electrophysiological correlate of synaptic plasticity), and 3) receptor biochemistry (by quantitative autoradiographic techniques which identify biological markers of the age- related memory loss). Finally, these investigators are examining the mechanism by which a new drug (pentoxifylling) appears to be capable of at least partially reversing this age-related memory loss. Research at this level contributes not only to our understanding of the processes by which learning and memory occur, but also provides insights into the basic physiological mechanisms by which these processes decline with age.