I'm an aging neuroscientist, interested in how we can prevent or repair the declines that occur during aging in learning and memory ability. I'm hoping to figure this out before I forget what the question is.
We've been characterizing changes in the expression of a receptor that is very important for the formation of memories, the N-methyl-D-aspartate (NMDA) receptor. This receptor uses glutamate as a transmitter.The NMDA receptor shows greater declines in binding of glutamate with increased age than any of the other glutamate receptors. We've found relationships between NMDA receptor binding and expressions of two NMDA receptor subunits, GluN2B (epsilon2, NR2B) and GluN2A (epsilon1, NR2A), during aging. We've also shown associations between age-related changes in NMDA binding densities and subunit expressions and declines in both working and reference memory ability.
We are continuing to characterize the changes that occur in the NMDA receptor with increasing age. We are currently examining whether increasing the expression of the GluN2B subunit or some of the splice variants of the GluN1 subunit is beneficial to memory in aged animals, how aging affects where the NMDA receptors are located within the neurons, and whether inflammation plays a role in the effects of aging on NMDA receptors. We are also trying to determine exactly what role NMDA receptors in the prefrontal cortex play in different forms of memory. Ultimately we want to discover the mechanisms underlying the age-related changes in the NMDA receptor.
In order to enhance the translation of our work, we have recently developed, in collaboration with Jimmy Zhong and Dr. Scott Moffat, Georgia Institute of Technology, a virtual water maze for testing human subjects. This task is designed to be similar to the water maze task that we use to assess memory in mice. We believe that this will enhance our ability to transition from screening interventions in mice to testing them in humans, by using the same task.
The lab's main goal is to find interventions into aging that will help to maintain the quality of life into old age. We're also interested in helping to better understand the function of the NMDA receptor in different brain regions.
Recently, we have also begun to examine the role of that the gut microbiota and high energy diets play in cognitive abilities. We have found that animals fed a high sucrose diet show deficits in early learning and those fed either a high fat or high sucrose diet have trouble with cognitive flexibility. Certain alterations in the composition of the gut microbiota showed relationships to these cognitive problems. We are pursuing evidence of whether these deficits are due to diet alone or the microbiota.
This is the picture from our laboratory T-shirt.
It was designed by Dr. Anna D. Fails, Dept. of Biomedical Sciences,
College of Veterinary Medicine & Biomedical Sciences, Colorado State University.