Whole-cell recordings from optic tectal neurons in Xenopus tadpoles were used to study the maturation of a glutamatergic synapse. The first glutamatergic transmission is mediated only by N-methyl-D-aspartate (NMDA) receptors and is silent at resting potentials. More mature synapses acquire transmission by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. This maturational program is mimicked by postsynaptic expression of constitutively active calcium-calmodulin-dependent protein kinase II (CaMKII). Newly formed synapses may be silent unless sufficient depolarization is provided by coincident activity that could activate postsynaptic CaMKII, resulting in the appearance of AMPA responses.