Abstract
The brain has evolved mechanisms to dynamically modify blood flow, enabling the timely delivery of energy substrates in response to local metabolic demands. Several such neurovascular coupling (NVC) mechanisms have been identified, but the vascular signal transduction and transmission mechanisms that enable dilation of penetrating arterioles (PAs) 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 NVC. Recent evidence suggests that capillaries play a major role in sensing neural activity and transmitting signals to modify the diameter of upstream vessels. Thin-strand pericyte cell bodies and processes cover around 90% of the capillary bed, and here we show that these cells play a central role in sensing neural activity and generating and relaying electrical signals to arterioles. We identify a K(ATP) channel-dependent neurovascular signaling pathway that is explained by the recruitment of thin-strand pericytes and we deploy vascular optogenetics to show that currents generated in individual thin-strand pericytes are sent over long distances to upstream arterioles to cause dilations in vivo. Genetic disruption of vascular K(ATP) channels reduces the arteriole diameter response to neural activity and laser ablation of thin-strand pericytes eliminates the K(ATP)-dependent component of NVC. Together, our findings indicate that thin-strand pericytes sense neural activity and transform this into K(ATP) channel-dependent electrometabolic signals that inform upstream arterioles of local energy needs, promoting spatiotemporally precise energy distribution.