A FluoroNissl dye identifies pericytes as distinct vascular mural cells during in vivo brain imaging

Pericytes and smooth muscle cells are integral components of the brain microvasculature. However, no techniques exist to unambiguously identify these cell types, greatly limiting their investigation in vivo. Here we show that a fluorescent Nissl dye (NeuroTrace 500/525) labels brain pericytes with exquisite specificity allowing high-resolution optical imaging in the live mouse. We demonstrate that capillary pericytes are a population of mural cells with distinct morphological, molecular, and functional features that do not overlap with pre-capillary or arteriolar smooth-muscle actin-expressing cells. The remarkable specificity for dye uptake suggests that pericytes have molecular transport mechanisms not present in other brain cells. We demonstrate feasibility for longitudinal pericyte imaging during microvascular development and aging and in models of brain ischemia and Alzheimer’s disease. The ability to easily label pericytes in any mouse model opens the possibility of a broad range of investigations of mural cells in vascular development, neurovascular coupling and neuropathology.