Sleep slow-wave activity (SWA, electroencephalogram [EEG] power between 0.5 and 4.0 Hz) is homeostatically regulated, increasing with wakefulness and declining with sleep. Sleep SWA is thought to reflect sleep need, but the mechanisms of its homeostatic regulation remain unknown. Based on a recent hypothesis, we sought to determine whether a decrease in cortical synaptic strength can account for changes in sleep SWA.