ReviewAMPA Receptor Trafficking at Excitatory Synapses

1999) studies showing that some synapses contain Excitatory synapses in the CNS release glutamate, NMDA receptors but no AMPA receptors. which acts primarily on two types of ionotropic recepIn addition to LTP, synapses can also undergo longtors: AMPA receptors and NMDA receptors. AMPA term depression (LTD). A more modest and prolonged receptors mediate the postsynaptic depolarization activation of NMDA receptors induces LTD, which, like that initiates neuronal firing, whereas NMDA receptors LTP, involves modification of AMPA receptor function. initiate synaptic plasticity. Recent studies have emAMPA receptor modulation in LTP and LTD comes in phasized that distinct mechanisms control synaptic two forms. First, there is evidence for covalent modificaexpression of these two receptor classes. Whereas tion of synaptic AMPA receptors. Second, activity can NMDA receptor proteins are relatively fixed, AMPA drive receptor proteins into the synapse during LTP or receptors cycle synaptic membranes on and off. A remove them from the synapse during LTD. large family of interacting proteins regulates AMPA Contrasting Dynamics of AMPA and NMDA receptor turnover at synapses and thereby influences Receptors during LTP synaptic strength. Furthermore, neuronal activity conMost studies have found a selective increase in the trols synaptic AMPA receptor trafficking, and this dyAMPA excitatory postsynaptic currents (EPSCs) and litnamic process plays a key role in the synaptic plastictle change in NMDA receptor EPSCs following LTP ity that is thought to underlie aspects of learning (Kauer et al., 1988; Muller et al., 1988). This strongly and memory. supports a postsynaptic expression mechanism and