The overall goal of our research is to understand the control of cerebral blood flow in physiological and small vessel disease conditions, with a special interest in the interaction between neural activity and the parenchymal microvasculature. Our early studies focused on the control of smooth muscle and endothelial cell function by ion channels, providing some of the first measurements of membrane potential, calcium signaling, and diameter imaging of mouse pressurized intracerebral arterioles. Developing these approaches in mouse microcirculation was a tour de force that lets us to use genetic mouse models and investigate potential treatments for cerebrovascular diseases. The emerging view from our work on CADASIL, an archetypal monogenic form of small vessel disease of the brain, is that fundamental alterations in extracellular matrix proteins disrupt the ion channel repertoire controlling vascular reactivity, and then cerebral hemodynamics, at a very early stage. In our more recent work on neurovascular coupling, the mechanism sustaining functional hyperemia, we established brain capillaries as an active sensory web detecting neural activity and communicating it to upstream arterioles in the form of vasodilatory signals to match the local metabolic demands. Currently, our work is aimed at understanding the disruption of neurovascular coupling in disorders involving extracellular matrix protein alterations to shed light on vascular dementia.