One intracellular signaling pathway with significant implications in neuronal cell biology is modulated by the serine-threonine kinase Akt. Akt is an evolutionarily conserved serine-threonine kinase that promotes cell growth and survival in neurons and other cell types. Akt kinase activity is increased by signals as diverse as growth factor receptor stimulation at the plasma membrane and stimulation of different brain regions, and it is also enhanced following the acquisition of new memories. In support of a far-reaching role for intact Akt signaling in human cognition, coding variations have been described in individuals suffering from mental diseases. These findings have led us to our working hypothesis that impaired Akt signaling is involved in brain processes associated with cognition. To address this hypothesis experimentally, we are examining genetically modified mouse models of altered Akt signaling using neuronal cell biology, biochemistry and physiology, and also in behavioral paradigms.