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

Area of Science:

• Neuroscience
• Vascular Biology
• Systems Biology

Background:

• Cerebral blood flow (CBF) regulation is crucial for neural function, occurring at local and global scales.
• Local CBF is managed by neurovascular coupling, but global coordination mechanisms are poorly understood.

Purpose of the Study:

• To investigate the role of the locus coeruleus-norepinephrine (LC-NE) system in global cerebral blood flow regulation.
• To elucidate the mechanisms underlying brain-wide vascular control coordinated by the LC-NE system.

Main Methods:

• In vivo whole-brain monitoring of neurovascular components in larval zebrafish.
• Analysis of LC-NE system signaling pathways to pericytes (capillary and arteriole-end).

Main Results:

• The LC-NE system acts as a central hub for global neurovascular communication.
• LC-NE signaling drives patterned pericyte activity from capillaries to arterioles, causing brain-wide vasoconstriction.
• This patterned activity is mediated by direct norepinephrine and indirect glia-relayed actions.

Conclusions:

• A spatiotemporal mechanism for global vascular control orchestrated by the LC-NE system has been uncovered.
• The LC-NE system aligns brain vascular states with arousal states to support sustained behavioral performance.