Neurovascular Interactions That Drive Nervous System Function

Major current vascular research questions:

What controls the molecular interplay between the vasculature and specialized neuronal populations?

How to blood vessels develop proper distributions within the central nervous system to enable brain function?

How do declines in vascular function impact brain diseases?

Neuromodulators can alter vasculature growth and function.  Blood vessels in the CNS support and are required for neural activity that underlies all CNS function. In turn, the growth and function of CNS vessels are regulated by reciprocal relationships between cells that comprise the vascular unit. Surprisingly, we find that the neuro-modulator dopamine restricts vascular development via temporally limited production by an unexpected neuron subset. In ongoing work, we seek to understand whether dopamine has a direct or indirect effect on vessels and determine the mechanisms by which neuron subtypes temporally produce dopamine.

Vascular contributions to brain disease pathology. Neurovascular coupling enables the vasculature to dynamically respond to neurons so that local energy demand is met with a precisely tuned local energy supply. Neurovascular coupling dysfunction is a prominent feature of Alzheimer’s and other brain diseases. While these changes are well documented at the descriptive level, little is known about their cellular or molecular bases. Also unknown is whether restoring neurovascular coupling would prevent or reverse disease pathology. Thus, the goals of these projects are to decipher the structural and molecular pathways through which Alzheimer’s and other diseases induce neurovascular coupling defects  as a basis for therapeutics to enhance CNS resiliency. 

Pericytes biology and function. Pericytes are responsible for local neuro-vascular coupling outcomes and they directly interact with both perivascular microglia as well as blood vessels in part through unique structures called pericyte nanotubes. The goals of these projects are to determine how and why these nanotubes tubes form, asses the contribution of other cells types to their maintenance and loss, and decipher the nature of the molecular cross talk between pericytes and non-pericyte cells.