Globally patterned locus coeruleus-norepinephrine neuron-pericyte coupling orchestrates brain-wide vascular dynamics

The brain regulates its blood supply at both local and global scales to ensure proper neural functions. While local cerebral blood flow (CBF) is regulated by regional neural activities via neurovascular coupling, how CBF is globally coordinated remains largely unclear. Leveraging in vivo whole-brain monitoring of multiple neurovascular components in larval zebrafish, we demonstrate that the locus coeruleus-norepinephrine (LC-NE) system, a key arousal node in vertebrates, functions as a central hub in global neurovascular communication through driving capillary-to-arteriole patterned activities of brain-wide pericytes. Such patterned activities arise from LC-NE signaling to capillary and arteriole-end pericytes, preferentially via direct NE and indirect glia-relayed actions, respectively. This LC-NE neuron-pericyte coupling causes brain-wide patterned vasoconstriction and thereby facilitates global CBF allocation, supporting sustained behavioral performance. Thus, our findings uncover a spatiotemporal mechanism of global vascular control and suggest a role for the LC-NE system in aligning brain vascular states with arousal states.