Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate.
Salient stimuli that modify behavior induce transcription of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and transport Arc mRNA into dendrites, suggesting that local Arc translation mediates synaptic plasticity that encodes such stimuli. Here, we demonstrate that long-term synaptic depression (LTD) in hippocampal neurons induced by group 1 metabotropic glutamate receptors (mGluRs) relies on rapid translation of Arc. mGluR-LTD induction causes long-term increases in AMPA receptor endocytosis rate and dendritic synthesis of Arc, a component of the AMPAR endocytosis machinery. Knockdown of Arc prevents mGluRs from triggering AMPAR endocytosis or LTD, and acute blockade of new Arc synthesis with antisense oligonucleotides blocks mGluR-LTD and AMPAR trafficking. In contrast, LTD induced by NMDA receptors does not persistently alter AMPAR endocytosis rate, induce Arc synthesis, or require Arc protein. These data demonstrate a role for local Arc synthesis specifically in mGluR-LTD and suggest that mGluR-LTD may be one consequence of Arc mRNA induction during experience.
Waung
Maggie W
MW
Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Pfeiffer
Brad E
BE
Nosyreva
Elena D
ED
Ronesi
Jennifer A
JA
Huber
Kimberly M
KM
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019921:Biotinylation / Q000379:methods; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D014176:Protein Biosynthesis / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
D003598:Cytoskeletal Proteins; D049452:Green Fluorescent Proteins; D008734:Methoxyhydroxyphenylglycol; D009419:Nerve Tissue Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D018091:Receptors, AMPA; C092069:activity regulated cytoskeletal-associated protein; C010117:3,4-dihydroxyphenylglycol