Discovering neural underpinnings of age-related changes in perceptual and value-based decision-making

Our ability to learn, remember and make decisions changes with age. Older mice, for example, take longer to learn new tasks and don’t perform as well as their younger counterparts. We aim to discover how the neural circuits that support learning, attention and decision-making evolve with age and how these changes contribute to age-related changes in behavior. Our hypothesis is that many age-related differences in behavior and learning capacity arise not from neurodegeneration but from active remodeling of neural circuits. To test this hypothesis, we will track age-related changes in mice all the way from gene expression to complex behavior. We will use an automated system to characterize spontaneous behavior and to measure learning and expert performance on two complementary tasks that have already been thoroughly tested in young adult animals. Next, we will measure and manipulate neural activity in both cortical and subcortical structures to determine which brain areas mirror changes in behavior and when these changes are most prominent during the life span. We will also track the synaptic, cellular and wiring changes that occur in these brain areas during healthy aging. In addition to exploring neural changes, we will examine how glial cells contribute to age-related decline. Previous research in our group has shown that a set of genes active in glia may drive some of these changes. We will determine if silencing these genes can prevent age-related decline in learning and decision-making. Taken together, these approaches will greatly advance our understanding of the neural underpinnings of age-related changes in synapses, circuits and behavior.