Brief metabotropic glutamate receptor (mGluR) activation leads to plasticity of AMPA receptor (AMPAR) synaptic transmission. To test whether mGluR-mediated plasticity of AMPAR transmission is influenced by recent neuronal activity, we manipulated visual activity in Xenopus laevis tadpoles in vivo. We compared mGluR-mediated plasticity of AMPAR transmission in optic tectal cells of tadpoles with low levels of previous synaptic activity (overnight in the dark) to transmission in neurons from animals after 4 h of constant visual stimulation. mGluR-mediated plasticity of AMPA transmission was significantly decreased in neurons with recent activity. We tested the role of the activity-regulated mGluR scaffolding protein Homer1a in modulating mGluR-mediated changes in AMPAR transmission. We found that, by changing the ratios of Homer 1a to Homer 1b in vivo, by either induction of endogenous Homer1a by visual activity or ectopic expression of Homer1a or Homer1b, we could change the direction of mGluR-mediated plasticity. This is the first evidence that mGluR-mediated changes in AMPA transmission can be regulated by Homer proteins in response to physiologically relevant stimuli.