A Role for Dendritic mGluR5-Mediated Local Translation of Arc/Arg3.1 in MEF2-Dependent Synapse Elimination
Year: 2014
Type: article
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.
Source: Cell Reports
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Awards: Regulation of experience-dependent cortical circuit development by MEF2C and genes linked to neurodevelopmental disorders, REGULATION OF SYNAPSE ELIMINATION BY FMRP, Mechanisms of mGluR5 function and dysfunction in mouse autism models, G5154890648, G5807927714, G5854036800, Cortical circuit changes and mechanisms in a mouse model of Fragile X Syndrome, Basic Science Training Program in the Neurobiology of Mental Illness, INVESTIGATION OF PROTOCADHERIN-10 IN MEF2- AND FMRP-MEDIATED SYNAPSE ELIMINATION
OpenAlex ID: W2054753187