Ultrastructure of Precapillary Sphincters and the Neurovascular Unit

Abstract Neurons communicate with vasculature to regulate blood flow in the brain. The cells that maintain this are collectively named the neurovascular unit (NVU). This communication, known as neurovascular coupling, is thought to involve astrocytes or molecules that can pass through the astrocytic endfeet. However, the exact mechanism is still unclear. Using large 3D electron microscopy datasets, we can now study the entire NVU in context. In this study, I provide evidence for the role of precapillary sphincters as a hub for neurovascular coupling and endothelial transcytosis, as well as the role of collagen synthesized by fibroblasts in strengthening first-order capillaries. I also show how astrocytic endfeet form a barrier for fluid flow and how the microvasculature of the cortex is not innervated but is surrounded by a surprising organization of parenchymal neuronal processes around penetrating arterioles and arterial-end capillaries in both mouse and human brains. Significance statement The neurovascular unit (NVU) is made up of various types of cells, including neurons, astrocytes, and endothelial cells, which work together to regulate blood flow in response to changes in neural activity. This process, known as neurovascular coupling, is crucial for ensuring that the brain receives an adequate supply of oxygen and nutrients. This study suggests a novel organization of the NVU and neurovascular coupling. Through ultrastructural analysis, I was able to identify previously unknown relationships between the different types of cells in the NVU. These findings provide new insights into the structure of the NVU and how it functions, which may help researchers develop new strategies for preserving cognitive function and promoting healthy aging.