Altogether, the results presented here demonstrate that microglia and type I IFN signaling have a key role in the electrophysiological and memory phenotypes of an animal model of TSC, a result consistent with the hypothesis that abnormal type I IFN signaling in microglia is responsible for abnormal LTP and for hippocampal memory deficits in Tsc2+/− mice. This evidence concerns the gene TSC2 and tuberous sclerosis.