Long-term potentiation (LTP) is a persistent strengthening ofsynaptic transmission in the brain and is arguably the mostcompelling cellular and molecular model for learning and memory.Previous work found that both AMPA receptors and exogenouslyexpressed kainate receptors are equally capable of expressing LTP,despite their limited homology and their association with distinctauxiliary subunits, indicating that LTP is far more promiscuousthan previously thought. What might these two subtypes ofglutamate receptor have in common? Using a single-cell molecularreplacement strategy, we demonstrate that the AMPA receptorauxiliary subunit TARP γ-8, via its PDZ-binding motif, is indispens-able for both basal synaptic transmission and LTP. Remarkably,kainate receptors and their auxiliary subunits Neto proteins sharethe same requirement of PDZ-binding domains for synaptic traf-ficking and LTP. Together, these results suggest that a minimalpostsynaptic requirement for LTP is the PDZ binding of glutamatereceptors/auxiliary subunits to PSD scaffolding proteins.