Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis

Cerebellar long-term depression (LTD) is a cellular model system of informa tion storage that may underlie certain forms of motor learning. While cereb ellar LTD is expressed as a selective modification of postsynaptic AMPA rec eptors, this might involve changes in receptor number/distribution, unitary conductance, kinetics, or glutamate affinity. The observation that GluR2-c ontaining synaptic AMPA receptors could be internalized by regulated clathr in-mediated endocytosis suggested that this process could underlie LTD expr ession. To test this hypothesis, we postsynaptically applied dynamin and am phiphysin peptides that interfere with the clathrin endocytotic complex and found that they blocked LTD expression in cultured Purkinje neurons. In ad dition, induction of LTD and attenuation of AMPA responses by stimulation o f clathrin-mediated endocytosis occluded each other. These findings suggest that the expression of cerebellar LTD requires clathrin-mediated internali zation of postsynaptic AMPA receptors.