Mechanisms underlying neurovascular coupling:

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A sector of the brain is active when a person is reading, listening to music, or doing any other activity. This activated region of the brain needs more nutrients and oxygen that come from the blood. To regulate this increase in blood supply associated with neuronal activity, a phenomenon called NEUROVASCULAR COUPLING, the brain uses complex mechanims. These mechanisms underlying neurovascular coupling have been the subject of enquiry for more than a century, and numerous vasoactive factors derived from neurons and ASTROCYTES have been implicated in neurovascular coupling. Astrocytes are a specific type of brain cells which comprises about half the brain but were thought to play no role in brain processes. Recent important discoveries showed that astrocytes are involved in neurovascular coupling by linking, anatomically and functionally, the brain's neurons to blood vessels. In the present proposal, we HYPOTHETIZE that carbon monoxide (CO) and nitric oxide (NO), two gases derived from astrocytes and neurons respectively, induce vasodilation by acting on astrocytes. This concept is very innovative because it is generally assumed that these two gases diffuse to the vasculature to directly induce a vasodilation. However, astrocytes are anatomically closer to the sites of NO and CO release and our very exciting preliminary results showed that NO increases calcium in astrocytes, a mechanism that induces vasodilation. We will study the effect of NO and CO on neurovascular coupling using isolated cells and tissues as well as living animals. The isolated cells and tissues will allow the understanding of mechanisms at the molecular level and the living animals will permit to verify the functional significance of the results we get from isolated cells or tissues. This approach will give an integrated understanding of neurovascular regulation from molecular interactions to the whole animal.The LONG-TERM GOAL of the present proposal is to enhance our understanding of how neural activity is related to blood flow.