A brain vascular electrical network links capillary pericytes to arterioles and is recruited for neurovascular coupling
Authors: Isaacs Dominic , Xiang Liuriumin , Hariharan Ashwini , Longden Thomas 
Published: May 2024

The brain has evolved mechanisms to rapidly modify local vascular resistance near active neurons. This enables delivery of energy substrates and clearance of byproducts via the blood to meet the energetic demands of circuits engaged during cognitive and motor tasks. Collectively, the physiochemical processes governing the spatially precise blood flow changes that accompany neural activity are termed “neurovascular coupling”. Crucially, these blood flow changes are leveraged by functional brain imaging techniques in humans to evaluate disease processes and understand cognition. It is therefore imperative to understand in detail the interaction between neurons and vasculature in the brain. While several neurovascular coupling pathways have been identified and studied, there is still no consensus on the vascular signal transduction and transmission mechanisms that enable acute responses to vasoactive substances released by active neurons. Arteriolar diameter is viewed as a crucial control point for neurovascular coupling. The relatively sparse spatial arrangement of arterioles contrasts with the vast plexus of capillaries, suggesting that that the latter is well positioned to play a major role in sensing neural activity and transmitting signals to modify the state of contractile cells on upstream vessels. Thin-strand pericyte processes cover a large fraction of the capillary bed but the contributions of these cells to blood flow control are not understood and are controversial. Here, we provide evidence that thin strand pericytes in the deep capillary bed play a role in neurovascular coupling by sensing neural activity and rapidly relaying electrical signals to arterioles. We identify a KATP channel-dependent neurovascular signaling pathway that can be explained by the recruitment of capillary pericytes. We developed a vascular optogenetics approach to show that membrane currents generated in single thin-strand pericytes are rapidly sent over long distances to penetrating arterioles in vivo. We demonstrate that genetic disruption of the KATP channel reduces the neurovascular coupling arteriole diameter response and laser ablation of pericytes eliminates KATP-dependent neurovascular coupling. Overall, our work suggests that the thin-strand pericytes of the capillary bed actively sense neural activity and integrate this into electro metabolic signals that inform arterioles of local energy needs ensuring spatiotemporal specificity in the availability of energy substrates like glucose, lactate, and oxygen. This work was supported by the NIH T32 Interdisciplinary Training Program in Cardiovascular Disease at The University of Maryland School of Medicine (ITCVD-T32), and NIH grants 1R01AG066645, 5R01NS115401, and 1DP2NS121347. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.