title: Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis.
abstract: Cerebellar long-term depression (LTD) is a cellular model system of information storage that may underlie certain forms of motor learning. While cerebellar LTD is expressed as a selective modification of postsynaptic AMPA receptors, this might involve changes in receptor number/distribution, unitary conductance, kinetics, or glutamate affinity. The observation that GluR2-containing synaptic AMPA receptors could be internalized by regulated clathrin-mediated endocytosis suggested that this process could underlie LTD expression. To test this hypothesis, we postsynaptically applied dynamin and amphiphysin peptides that interfere with the clathrin endocytotic complex and found that they blocked LTD expression in cultured Purkinje neurons. In addition, induction of LTD and attenuation of AMPA responses by stimulation of clathrin-mediated endocytosis occluded each other. These findings suggest that the expression of cerebellar LTD requires clathrin-mediated internalization of postsynaptic AMPA receptors.
authors.affiliation: Division of Pathology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Y T
authors.initials: YT
authors.lastname: Wang
authors.forename: D J
authors.initials: DJ
authors.lastname: Linden
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002966:Clathrin / Q000502:physiology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004705:Endocytosis / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D016318:Quisqualic Acid / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000502:physiology*
chemical_list: D002614:Chelating Agents; D002966:Clathrin; D018690:Excitatory Amino Acid Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D018091:Receptors, AMPA; D004533:Egtazic Acid; D007334:Insulin-Like Growth Factor I; D016318:Quisqualic Acid; D017526:Receptor, IGF Type 1; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid