作者
Dominic P Isaacs, Liuruimin Xiang, Ashwini Hariharan, Thomas A Longden
发表日期
2024/4/5
简介
The brain has evolved mechanisms to dynamically modify local blood flow, thus enabling the timely delivery of energy substrates and the rapid clearance of byproducts in response to the highly fluctuating metabolic demands of cognition and behavior. Several such neurovascular coupling mechanisms have been identified, but vascular signal transduction and transmission mechanisms that enable acute dilation of penetrating arterioles remote from sites of increased neuronal activity are unclear. Given the exponential relationship between vessel diameter and blood flow, tight control of arteriole membrane potential and diameter is a crucial aspect of neurovascular coupling. However, the relatively sparse spatial arrangement of arterioles contrasts with the vast plexus of capillaries, and recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the contractile state of mural cells on upstream vessels. Thin-strand pericyte processes cover around 90% of the capillary bed but their specific contributions to blood flow control are not understood. We hypothesized that thin-strand pericytes could play a role in sensing and transmitting blood flow control signals from neurons back to the electromechanical controller of blood flow , upstream PA and contractile pericytes. We first wondered whether we could probe for the existence of a functional vascular relay between pericytes and arterioles using focal optogenetics. To do this we developed a mouse line expressing ArchT-EGFP optically driven proton pump in mural cells (shown below). We targted pericytes in this mouse with focal 561 nm laser to …