Neurons are structurally complex: most have a single long axon that transmits electrical signals and multiple branching dendrites that receive input from neighboring cells. For many neurons, these dendrites are additionally covered in small dendritic spines that integrate incoming information. Although alterations in the shape or number of dendritic spines are implicated in neurological disorders, little is known about whether these structures have a specialized role in transmitting electrical information independent from their associated dendrite. In the Yuste laboratory, we have developed a method that uses two-photon microscopy and voltage-sensitive fluorescent proteins to measure the electrical activity of dendritic spines in vivo. Combining this approach with state-of-the-art techniques in molecular genetics, neurophysiology, and optogenetics, we are testing whether electrical compartmentalization of spines exists in vivo, and if this is relevant for dendritic computation.