Neural activity increases cerebrospinal fluid influx and waste removal in the glymphatic system*

The flow of cerebrospinal fluid (CSF) fluid through perivascular spaces (PVSs) is an essential part of the glymphatic system, which promotes metabolic waste clearance in the brain. Neuronal activation leads to vessel dilation, increased blood flow, and an increase in local consumption of energy and production of metabolites. Because neural activity is linked to the production of metabolic waste, we examined whether neuronal activation induced by whisker stimulation also increases glymphatic fluid transport and thereby boosts the removal of metabolic waste. We studied fluid flow in the brains of anesthetized mice using a two-photon microscope, dye visualization, and particle tracking. We found that whisker stimulation increases blood flow and CSF inflow. Particle tracking showed that vessel dilation decreases the CSF downstream velocity but also increases outward flow away from the dilating arterial wall. Increased CSF tracer accumulation and later clearance were noted within the activated hemisphere compared with the opposite hemisphere, demonstrating that neural activity increases glymphatic influx and waste removal. In comparison, laser-induced constriction of the vessel in transgenic mice revealed that  pure vessel constriction in the absence of neural activation does also increase the CSF volumetric flow and drives backflow in downstream regions.