Identification of the molecular and cellular events that occur in the aging central nervous system is a critical area of basic research. The state of the aging central nervous system is largely dependent on the balance between functional losses and intrinsic biological mechanisms that serve to compensate for such losses. This series of studies proposes to study excitatory amino acid (EAA) networks, because they are central to the balance between function and pathology. Dysfunction of EAA receptors would compromise learning and plasticity; their preservation would serve to maintain function; and their overactivation would promote cell death. By examining this system in models of normal aging and animal lesions, it will be possible to identify changes occurring at the level of the synapse that represent key events in plasticity mechanisms, neuronal degeneration, and normal aging. This series of experiments proposes to examine the relationship between EAA receptors and transporters in the mature and aged brain of rodents and non-human primates. Failures in one or more of these components would be expected to compromise function and perhaps contribute to the decline in cognitive abilities with aging. Some changes in the aged brain may represent plastic reactions attempting to compensate for cell loss. Such a response is observed in the young rodent brain where an entorhinal lesion causes axon sprouting and receptor plasticity in the hippocampal formation. Accordingly, receptor changes in the denervated hippocampus of mature animals will be compared with those in the aging brain. By examining each of the EAA components in the normal brain and during reactive synaptogenesis, a clearer picture of the functional and compensatory abilities of the aged brain can be derived.
