Grant: Operating Grant

Brain cells are normally protected by a mechanism that delivers enhanced blood flow to areas that have increased demand. Defects in this protective mechanism are assocaited with development of dementias including Alzheimer's Disease. Our lab has identified a protein inside the lining of brain blood vessels that reponds to neurotransmitters released during brain activity by increasing the vessel diameter and, consequently, the amount of blood that can flow through the vessel. This is the first description of this mechanism. Thus our proposal is to thoroughly characterize the structural and functional characteristics of this receptor target, and then to examine how brain cells communicate with this blood vessel protein in intact brain models, including a) thin slices of brain that contain both brain cells and blood vessels in native form in a complex known as the "neurovascular unit," and b) whole animal brain using intricate surgical and imaging procedures. These experiments will produce results with important implications for all research streams involving this protein, including stroke, brain inflammation and Alzheimer's Disease