FIGURE 22-43 AMPA glutamate receptor trafficking during hippocampal LTP and LTD. (a) In the basal state, AMPA receptors (black) traffic constitutively to and from the plasma membrane of the postsynaptic compartment via recycling endosomes. Receptors are delivered to the plasma membrane lateral to the postsynaptic density via exocytosis, and are internalized by clathrin-mediated endocytosis into recycling endosomes. In the postsynaptic density, the AMPA receptors are stabilized by interactions with proteins, including transmembrane AMPA receptor regulatory proteins (TARPS, not shown). (b) Following induction of long-term potentiation (LTP) at glutamatergic synapses, there is an increase in the exocytosis of AMPA receptors and an increase in their diffusion into the postsynaptic density. This results in an increase in the number of AMPA receptors on the postsynaptic membrane, and an increase in the postsynaptic response to a given amount of glutamate release from the presynaptic neuron. (c) Following induction of long-term depression (LTD) of glutamatergic synapses, there is an increase in the diffusion of AMPA receptors out of the postsynaptic density and in their internalization into recycling endosomes. This results in a decrease in the number of AMPA receptors on the postsynaptic membrane, and a decrease in the postsynaptic response to a given amount of glutamate release from the presynaptic neuron. Regulated trafficking of AMPA receptors provides one molecular mechanism underlying the activity-dependent changes in synaptic strength that accompany synaptic plasticity and memory. See J. D. Shepherd and R. L. Huganir, 2007, Ann. Rev. Cell Dev. Biol. 23:613–643.