Grant: Discovery Grants Program - Individual

How does the brain work? Recent theory suggests our brains continually use memory to make predictions about the world, adapting our behavior to our expectations. What happens when prediction fails? When circumstances change? When the unexpected occurs? Our research program focuses on a brain area, the locus coeruleus, which responds when prediction fails, and which projects broadly throughout the brain, giving it a privileged role in helping us adapt to change. Our recent studies reveal that activity in this area acts to suppress old memory and enhance attention to the information that needs to be incorporated into new memory to improve our ability to predict. We have shown that activity in the locus coeruleus triggers a novel mechanism for creating memory. We propose now to more fully characterize this novel mechanism. We want to know how long memory supported by the locus coeruleus can last, whether sleep is important for the locus coeruleus memory effect to occur and what happens to such memory when the locus coeruleus is repeatedly activated. We also want to better describe the effects on attention and old memory suppression induced by locus coeruelus activity. We expect that different brain areas might be affected differently depending on whether they are primarily processing current sensory inputs or memories. We want to understand how locus coeruleus activity affects individual cell types in the brain in order to know how it achieves its functions and to gain additional insights into how information and memories are represented in our brains. We have a new tool based on genetic engineering that will allow us to examine the connections of the locus coeruleus with cells throughout the brain. We also propose to study the role of the locus coeruleus in generating new adaptive behavior, both by blocking its actions and by correlating its effects on brain circuits with learning. Taken together these studies will take us further into an understanding of how the brain works to permit us to adapt successfully to the unexpected.