Cellular Control of Brain Capillary Blood Flow: In Vivo Imaging Veritas.

The precise modulation of regional cerebral blood flow during neural activation is important for matching local energetic demand and supply and clearing brain metabolites. Here we discuss advances facilitated by high-resolution optical in vivo imaging techniques that for the first time have provided direct visualization of capillary blood flow and its modulation by neural activity. We focus primarily on studies of microvascular flow, mural cell control of vessel diameter, and oxygen level-dependent changes in red blood cell deformability. We also suggest methodological standards for best practices when studying microvascular perfusion, partly motivated by recent controversies about the precise location within the microvascular tree where neurovascular coupling is initiated, and the role of mural cells in the control of vasomotility. In vivo optical imaging studies in rodents over the past two decades have significantly advanced the understanding of cellular mechanisms of neurovascular coupling. Rapid changes in red blood cell deformability and blood rheology due to fluctuations in oxygen levels can increase capillary cell flux prior to microvascular dilation. We review in vivo evidence indicating that activity-dependent changes in regional blood flow are mediated by smooth muscle cell contractility in arterioles but not by pericytes. Technical recommendations are provided for reproducible studies of neurovascular coupling in vivo and proper functional characterization of pericytes and smooth muscle cells. [ABSTRACT FROM AUTHOR]