Control of low flow regions in the cortical vasculature determines optimal arterio-venous ratios

The energy demands of neurons are met by a constant supply of glucose and oxygen via the cerebral vasculature. The cerebral cortex is perfused by dense, parallel arterioles and venules, consistently in imbalanced ratios. Whether and how arteriole-venule arrangement and ratio affect the efficiency of energy delivery to the cortex has remained an unanswered question. Here, we show by mathematical modeling and analysis of the mapped mouse sensory cortex that the perfusive efficiency of the network is predicted to be limited by low-flow regions produced between pairs of arterioles or pairs of venules. Increasing either arteriole or venule density decreases the size of these low-flow regions, but increases their number, setting an optimal ratio between arterioles and venules that matches closely that observed across mammalian cortical vasculature. Low-flow regions are reshaped in complex ways by changes in vascular conductance, creating geometric challenges for matching cortical perfusion with neuronal activity.