Blood flow patterns in mice are regulated by interpericyte tunneling nanotubes connecting functionally-opposite neuronal areas

Abstract Functioning of the central nervous system is critically dependent on precise blood delivery achieved through the formation of blood flow patterns or differences in flux between vessels. Nevertheless, how these blood flow patterns are generated is a fundamental question that is incompletely understood. Here, we show, in live imaging experiments on mice, that specialized pericytes connected via tunneling nanotubes regulate flux patterns by modulating the response of different capillaries in opposing ways, homogenizing blood flow, which is vital to supply functionally-opposite neuronal areas of the retina. We also identify that this capacity for stimulus-induced flow homogenization is lost after the ablation of interpericyte tunneling nanotubes via laser or during ischemia-reperfusion injury, a pathological condition that leads to widespread disruption of interpericyte tunneling nanotubes. These findings contribute to understanding neurovascular coupling and blood delivery in the retina.