Simulations of diffusion in the ECS of the CA1 hippocampus in WT and Has3^−/− mice. In these simulations, informed by our results on ECS parameters in individual layers, molecules were released for 1 ms from point sources in the center of each layer and allowed to diffuse. The same number of molecules was released into each layer. A, Images show concentration of diffusing molecules at 10 ms after the start of the release. Concentration is higher in the stratum pyramidale of Has3^−/− mice than in that of WT mice because of the reduced ECS volume fraction. Scale bar, 25 μm. B, Concentration versus time profiles at a distance of 5 μm from each point source (measured radially from axis of symmetry). Simulations show that the concentration of a substance released into stratum pyramidale will stay higher longer in Has3^−/− than in WT mice, and that a larger number of cells will simultaneously be exposed to the released substance.