Caveolae in CNS arterioles mediate neurovascular coupling

Area of Science:

• Neuroscience
• Vascular Biology
• Cellular Mechanisms

Background:

• Neurovascular coupling matches brain energy demand with blood flow, crucial for brain function and functional imaging.
• Impaired neurovascular coupling is linked to neurodegenerative diseases, yet its mechanisms are poorly understood.
• The conventional model posits neuronal or astrocyte-derived factors directly dilating arteries via smooth muscle cells.

Purpose of the Study:

• To investigate the cellular and molecular mechanisms of neurovascular coupling.
• To determine the role of arteriolar endothelial cells (aECs) in mediating neurovascular coupling.
• To elucidate the specific pathways involved, particularly the contribution of caveolae and the eNOS-NO pathway.

Main Methods:

• Simultaneous two-photon microscopy of neural activity and vascular dynamics in awake mouse barrel cortex during whisker stimulation.
• Acute genetic perturbations to eliminate caveolae in aECs and/or ablate endothelial NO synthase (eNOS).
• Assessment of neurovascular coupling function following genetic manipulations.

Main Results:

• Arteriolar endothelial cells (aECs) possess abundant caveolae, unlike other CNS endothelial cells.
• Eliminating caveolae specifically in aECs impaired neurovascular coupling, while sparing neighboring smooth muscle cells.
• Caveolae-mediated pathway in aECs is largely independent of the eNOS-NO pathway.
• Combined ablation of caveolae and eNOS completely abolished neurovascular coupling, indicating a major role for the caveolae pathway.

Conclusions:

• Arteriolar endothelial cells (aECs) play an active, crucial role in mediating neurovascular coupling.
• A novel caveolae-dependent pathway in aECs is a major contributor to regulating cerebral blood flow.
• This pathway actively relays signals from the central nervous system to smooth muscle cells for vasodilation.