The PI3K pathway controls important aspects of most physiological processes in the body, from embryonic development, to metabolism or cognitive function. This pathway is critical for neuronal differentiation and survival during brain development, and also for synaptic plasticity in mature neurons during adult life. Understandably, alterations in the PI3K function have been previously linked to mental disease, such as autism spectrum disorders. However, the specific mechanisms mediated by PI3K and their contribution to proper brain function have been difficult to untangle. During this presentation I will describe our latest results on PI3K signaling and its contribution to synaptic plasticity. Particularly, we will try to decipher how specific PI3K isoforms are differentially engaged in neurons and astrocytes during synaptic plasticity events, and their cognitive consequences.