Our research aims to further the understanding of how nervous and vascular systems develop, communicate, and work in concert to ensure proper brain function.
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While the brain represents 2% of the body mass, it uses 20% of the body's energy at rest. This use of energy depends upon oxygen and nutrients supplied from the bloodstream. Thus three unique features of supplying blood to the brain exist to ensure normal functioning of neural circuits. First, the brain is densely vascularized to meet its high metabolic demand. All neurons in the brain lie within 50 microns of the nearest capillary. Second, there is a functional coupling between neural activity and blood flow because during normal behavior, there are moment-to-moment changes in regional brain metabolic demand: these regions must be brought "online" quickly. Third, blood vessels in the brain comprise the blood-brain barrier that provides a tightly controlled environment free of toxins and pathogens and with proper chemical compositions for synaptic transmission. This ensures normal brain function.
The study of neurovascular interactions bridges the fields of neuroscience and vascular biology. Both the anatomical and functional aspects of neurovascular interactions are best seen under in vivo settings, such as the retina, basal ganglia system, and cortex. Thus, the main approaches we use in the lab are mouse genetics and more recently also zebra fish. These methodologies allow us to simultaneously observe both systems endogenously. More specifically, they allow us to use genetic manipulations to perturb one system and to observe the resultant consequences in the other. In order to identify and characterize the molecular signals underlying neurovascular interactions, we have also developed a variety of in vitro assays, screening strategies, and computational models. We then transfer the findings from these in vitro techniques back to the in vivosystem for validation. Finally, in order to establish the mechanisms that operate in vivo under normal physiological conditions, we have recently built a custom designed two-photon microscope to monitor neuro-vascular coupling and the blood-brain barrier permeability dynamics by imaging through cranial windows in awake mice. We aim to understand the neurovascular interactions from a molecular level to a systems level.