The immediate-early gene ARC is induced by neuronal activity (Lyford et al., 1995, Neuron 14:433). In addition, its mRNA is selectively transported to the activated portion of the dendritic arbor after high frequency synaptic stimulation (Steward et al., 1998, Neuron 21:741). We have previously shown that after the ARC protein reaches synaptic sites, it induces an AMPA-receptor specific synaptic depression. Moreover, drugs that affect protein phosphatase activity reduce the ARC-induced depression (Rial Verde et al., 2002, SFN 32nd Annual Meeting Abstract 839.5). The latter result suggests that ARC-induced depression may share some molecular mechanisms with other forms of synaptic depression. Here we investigate the AMPA-receptor subunit specificity of the ARC effect and further explore the molecular events that result in ARC-induced synaptic depression. Fluorescently-tagged proteins were expressed in CA1 pyramidal neurons of cultured hippocampal slices using a Sindbis virus expression system. The slices we...