Development of fiber-based all-optical system for neurovascular coupling mechanism study using optogenetics

Abstract

Optogenetics integrated with a variety of genetically encoded methods have been considered a very powerful technique for identifying neurovascular coupling mechanism. Recently, optogenetics has been applied to non-neuronal cells as well as neurons, to study the functions of various organs and tissues such as cardiovascular and bladder. However, the cerebrovascular network has a complicated environment in which cells and tissues with various features and functions coexist. In order to successfully apply optogenetics to study neurovascular coupling mechanism, it is necessary to develop not only optical stimulation techniques but also appropriate monitoring techniques. In addition, it has been very difficult to develop an appropriate optical system, since it is necessary to operate with the neurovascular network of a living animal maintained in the normal condition. Therefore, we have developed a fiber-based all-optical system that enables successful application of optogenetics to study neurovascular coupling mechanisms in living mouse. The developed optical system can perform rapid fluorescence imaging and optical stimulation at the same time, so it can measure various cell specific reactions and rapid blood flow that change after optical stimulation. In this study, we were able to observe changes in blood vessel diameter and blood flows caused by the cell activity of smooth muscle cells after selective optical stimulation using the developed all-optical system in SM22 alpha-ChR2 transgenic mice. Also, the developed all-optical system can be used to study cerebrovascular disease or hemodynamics using optogenetics in vivo.