Brain endothelial gap junction coupling enables rapid vasodilation propagation during neurovascular coupling

Area of Science:

• Neuroscience
• Vascular Biology
• Cell Biology

Background:

• Neural activation increases local blood flow via neurovascular coupling.
• This process requires coordinated vasodilation of cerebral arteries.
• The mechanisms governing signal propagation in cerebral vasculature are not fully understood.

Purpose of the Study:

• To investigate the role of endothelial gap junctions in propagating vasodilation signals during neurovascular coupling.
• To determine the molecular basis and functional significance of gap junction zonation in the brain vasculature.

Main Methods:

• Utilized optogenetics and visual stimuli in awake mice.
• Performed arterial endothelial cell type-specific gene deletion of connexins (Cx37 and Cx40).
• Assessed vasodilation propagation speed and spatial extent.

Main Results:

• Endothelial gap junction coupling facilitates long-range propagation of vasodilation.
• Gap junction composition is zonated along the arterio-venous axis, with arteries showing strongest coupling.
• Deletion of Cx37 and Cx40 in arterial endothelial cells abolished gap junction coupling and impaired vasodilation.
• Arterial endothelial gap junction coupling dictates the speed and extent of activity-induced vasodilation.

Conclusions:

• Endothelial gap junctions act as a critical signaling pathway for neurovascular coupling.
• These junctions enable efficient distribution of energy resources to active brain regions.
• Targeting endothelial gap junctions may offer therapeutic strategies for cerebrovascular disorders.