It is generally accepted that enduring changes in synaptic strength play a critical role in learning and memory. Long-term potentiation (LTP), a phenomenon in which brief repetitive activation of excitatory synapses results in a long lasting enhancement in synaptic transmission, is the leading cellular model for learning and memory. After more than a decade of debate, there is now an emerging consensus that the change in synaptic strength during LTP resides primarily in the postsynaptic density (PSD). More specifically accumulating evidence indicates that LTP recruits AMPA type glutamate receptors to the synapse. This research into synaptic plasticity has challenged the classical view of the synapse, in which receptors are firmly embedded in a rigid thicket of proteins in the PSD. Rather, the remarkably dynamic property of AMPA receptors rivals that usually associated with the presynaptic side of the synapse. Importantly, NMDA receptors, which intermingle with AMPA receptors, are relatively fixed components of the PSD. What accounts for the remarkable difference in the regulation of AMPA and NMDA receptors? This will be the focus of my talk. We have identified two proteins that play an essential role in AMPA receptor trafficking; PSD-95, a scaffolding protein, and stargazin, an auxiliary AMPA receptor subunit. The properties of PSD-95 make it an ideal candidate for determining the number of AMPA receptors that reside at a synapse. Stargazin, which binds both to PSD-95 and AMPA receptors, serves as the bridge. Stargazin is a member of a family of closely related proteins referred to as transmembrane AMPAR regulatory proteins (TARPs). In addition to their role in trafficking, TARPs also control the kinetics of synaptic currents. The possible roles for these proteins in activity-dependent trafficking of AMPA receptors will be discussed.