title: A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination.
abstract: Experience refines synaptic connectivity through neural activity-dependent regulation of transcription factors. Although activity-dependent regulation of transcription factors has been well described, it is unknown whether synaptic activity and local, dendritic regulation of the induced transcripts are necessary for mammalian synaptic plasticity in response to transcription factor activation. Neuronal depolarization activates the myocyte enhancer factor 2 (MEF2) family of transcription factors that suppresses excitatory synapse number. We report that activation of metabotropic glutamate receptor 5 (mGluR5) on the dendrites, but not cell soma, of hippocampal CA1 neurons is required for MEF2-induced functional and structural synapse elimination. We present evidence that mGluR5 is necessary for synapse elimination to stimulate dendritic translation of the MEF2 target gene Arc/Arg3.1. Activity-regulated cytoskeletal-associated protein (Arc) is required for MEF2-induced synapse elimination, where it plays an acute, cell-autonomous, and postsynaptic role. This work reveals a role for dendritic activity in local translation of specific transcripts in synapse refinement.
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Wilkerson
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Nien-Pei
authors.initials: NP
authors.lastname: Tsai
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Marina A
authors.initials: MA
authors.lastname: Maksimova
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10065, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Cabalo
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kristofer W
authors.initials: KW
authors.lastname: Loerwald
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10065, USA.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Dictenberg
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Gibson
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kimberly.huber@utsouthwestern.edu.
authors.forename: Kimberly M
authors.initials: KM
authors.lastname: Huber
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; C578936:Grm5 protein, mouse; D064326:MEF2 Transcription Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; C092069:activity regulated cytoskeletal-associated protein