Changes in sensory experience modify the function of the adult brain's neuronal circuits. This flexibility is reliant on the neurons' ability to change the strength of their connections. Most excitatory connections in the adult cerebral cortex are found on dendritic spines, protrusions from the dendrite that in vitro, and histological analyses, have been shown to be implicated in neuronal plasticity. The recent development of in vivo imaging techniques now provides the ability to explore experience-dependent structural plasticity in the adult brain; the changes in neuronal connectivity that accompany functional reorganizations of the sensory maps. Multi-photon laser scanning microscopy in transgenic mice expressing fluorescent proteins in cortical neurons shows that although the majority of spines is present throughout the imaging period of weeks a proportion of spines is transient, appearing and disappearing on a daily basis. A small fraction appears and stabilizes forming synapses, and this proportion can be affected by changes in sensory experience. This synapse formation occurs preferentially through the initial generation of a filopodial-like spine contacting an axonal bouton already present in the neuropil. The results implicate these specialized compartments of synaptic transmission as playing a central role in the functional reorganization of neuronal circuits.