Light flickering frequency-dependently (specifically at 40 Hz) increases glymphatic influx and efflux. Adenosine-A 2A R as the signaling pathway linking 40 Hz light flickering with enhanced glymphatic influx through the control of CBF, vasomotion and aquaporin-4: i) 40 Hz flicker enhancement of the glymphatic influx depends on astrocytic AQP4 polarization; ii) genetic deletion of ENT2 or of A 2A R abolishes the 40 Hz flicker effects on the glymphatic system; iii) A 2A R and aquaporin-4 are colocalized and functionally interact in astrocytes.
