These findings provide insights that help to contextualize previous reports of multi-domain cognitive deficits in the absence of the APP family, and in which single-cell in vitro electrophysiology and structural deficits were subtle and restricted to hippocampus.12,13 In so doing, our findings implicate APP proteins in excitatory neurons as playing an important physiological role in shaping spontaneous neuronal activity, which represents a fundamental property of the intact brain in vivo. This evidence concerns the gene APP and Cognitive impairment.