The goal of our research is to understand at the cellular and molecular level how synaptic connections form during development, how they are modified during learning and altered in disease. Most of the excitatory synaptic connections in the cortex occur on dendritic spines, tiny protrusions that extend from the dendritic membrane. Dendritic spines are highly dynamic during development both in vitro and in vivo; periods of high motility coincide with synapse formation. Spine motility, driven by actin dynamics, is thought to allow the postsynaptic neuron to explore and sample presynaptic partners. In addition, alterations of spine dynamics and stability have been observed during learning, leading to the hypothesis that these anatomical changes underlie the adaptive remodeling of cortical circuits. The identification and characterization of the molecules and mechanisms that control spine morphogenesis will be a crucial step toward understanding the formation and plasticity of cortical circuits. Our approach to this problem combines time-lapse imaging to observe nascent spine formation, and fluorescence recovery after photobleaching (FRAP) to measure protein dynamics, with molecular manipulations of synaptic proteins to decipher their roles in the growth of dendritic spines and synapses. In addition, we use electrophysiological measurements in combination with two-photon uncaging of glutamate to examine the function of nascent synapses at the single synapse level.