KDM6B interacts with Tau and is recruited by Tau to the promoters of Slc17a6 and Slc17a7, where it demethylates H3K27me3 to induce the expression of VGLUT1/2, leading to increased vesicle number, synaptic activity, dendritic spine density, and animal cognitive functions. KDM6B KO or Tau knockdown reduces VGLUT1/2 expression and vesicle number. Subsequently, it diminishes synaptic activity, spine density, and cognitive functions.