A model systems approach to age-related memory disorders

Memory deficits are common to virtually all forms of cognitive dysfunction and are central to disorders associated with aging. Animal models provide the opportunity to understand normal and pathologic memory in great detail. The model systems approach to the neurobiology of memory involves studying a well characterized learned response in a relatively simple and well controlled preparation. The best characterized mammalian model system is classical conditioning of the rabbit's eyeblink response. Using this preparation, significant progress has been made toward understanding the neurobiological systems and mechanisms involved in elaboration of the conditioned response. Using a well characterized model system such as classical eyeblink conditioning, it should be possible to both characterize the changes in learning and memory that accompany aging and to investigate their neural substrate. Our strategy for using the conditioned eyeblink preparation for studying age-related memory deficits is fourfold and includes investigating conditioning deficits in: (1) humans across the life-span, (2) rabbits across the life-span, (3) Alzheimer's disease patients, and (4) rabbits with aluminum-induced neurofibrillary degeneration. In this paper, we present exemplary data from each of these lines of research. If similar deficits occur in each of these groups, it may be possible to begin to form hypotheses about the neurobiology of age-related memory disorders.