A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination

Julia R. Wilkerson, Nien Pei Tsai, Marina A. Maksimova, Hao Wu, Nicole P. Cabalo, Kristofer W. Loerwald, Jason B. Dictenberg, Jay R. Gibson, Kimberly M. Huber

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35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1589-1600
Number of pages12
JournalCell Reports
Volume7
Issue number5
DOIs
StatePublished - Jun 12 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wilkerson, J. R., Tsai, N. P., Maksimova, M. A., Wu, H., Cabalo, N. P., Loerwald, K. W., Dictenberg, J. B., Gibson, J. R., & Huber, K. M. (2014). A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination. Cell Reports, 7(5), 1589-1600. https://doi.org/10.1016/j.celrep.2014.04.035