Abstract
The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes contribute to blood flow control. Using two-photon microscopy to observe and manipulate single capillary pericytes in vivo, we find their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than mural cells of upstream pial and pre-capillary arterioles. This slow, optogenetically-induced vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and relax towards baseline following optogenetically-induced vasoconstriction. In a complementary approach, optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux in capillaries lacking pericyte contact. Altogether these data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the capillary bed.
Footnotes
Funding: Our work is supported by grants to A.Y.S. from the NINDS (NS106138, AG063031, NS097775), the Dana Foundation, the American Heart Association (14GRNT20480366), Alzheimer’s Association NIRG award, and an Institutional Development Award (IDeA) from the NIGMS under grant number P20GM12345. D.A.H. is supported by awards NIH T32 GM08716, NIH - NCATS (UL1 TR001450 and TL1 TR001451), and NIH-NINDS F30NS096868.
Conflicts of interest: The authors have no financial or non-financial conflicts of interest.
Abbreviations
- α-SMA
- α-smooth muscle actin
- ACSF
- Artificial Cerebral Spinal Fluid
- ChR2
- Channelrhodopsin-2
- PDGFRβ
- Platelet-derived growth factor receptor β
- RBC
- Red blood cell
- SMC
- Smooth muscle cells
- YFP
- Yellow fluorescent protein