It has previously been shown that astrocytes can secrete factors that result in the formation of silent synapses, but whether they can induce formation of functional synapses was unknown. Exposure of purified retinal ganglion cell neurons to the astrocyte-secreted molecules glypican 4 (GPC4) and GPC6 was sufficient to induce functional synapses. Indeed, application of GPC4 to these neurons was sufficient to increase the postsynaptic surface expression of AMPA receptors and increase the amplitude and frequency of firing — all of which where attenuated in GPC4-deficient mice. These findings indicate that GPC4 and GPC6 have key roles in synapse development.