Dendritic spines are small, actin-rich protrusions that receive most of the excitatory synaptic inputs in the central nervous system. Spines are believed to mediate the synaptic plasticity that underlies cognitive functions, such as learning and memory. In accordance with this, pathological studies have revealed dendritic spine abnormalities in patients with intellectual disability, further emphasizing the central role of spines in integrating information flow in the brain. Despite its importance, the molecular mechanisms that regulate spine morphogenesis and synapse formation have only begun to be addressed. A special focus in my lab is to understand the signaling pathways that regulate the formation of dendritic spines and synapses in hippocampal neurons. Our work has led to the hypothesis that local activation of Rac, which is a member of the Rho family of small GTPases, is central for synapse formation and spine morphogenesis. Consistent with our work, three of seven recently identified genes mutated in nonsyndromic intellectual disability are involved in Rho family signaling. We are currently using live cell imaging, as well as biochemical and molecular techniques, to identify the signaling pathway(s) by which actin regulators modulate spine morphogenesis and synapse formation in hippocampal neurons.