Our human population is aging. The percentage of the population in this country that is over the age of 65 is projected to increase from 12.6% in 2005 to 20% by 2030. With this increase will come a rising financial burden to both families and society, unless we can prevent the declines that are currently associated with aging. Declines in brain functions during aging, including memory and cognitive flexibility, affect almost half of the human population over 65 years of age. This interferes with people’s quality of life as they get older. It also can become an economic burden, because they can no longer live independently. Pet animals can also experience these changes, which may limit their functional lifespan. These problems suggest that there is a decline in the optimal functioning of regions of the cerebral cortex and hippocampus. The N-methyl-D-aspartate receptor, a subtype of glutamate receptor, is highly expressed in these brain regions and plays a role in many of the functions that decline during aging. Our laboratory has found a selective vulnerability of the NMDA receptor to aging. This decline in NMDA receptors correlates with declines in memory function. We will be exploring the effects of drug or micronutrient intervention on these receptors during aging with the use of stereotaxic surgery, chronic drug administration, and/or behavioral testing using mice as our model system. We may also be examining the effects of interventions on receptor binding density, and subunit mRNA and protein expression with the use of receptor autoradiography, in situ hybridization and Western blots, respectively.