A Role for Dendritic mGluR5-Mediated Local Translation of Arc/Arg3.1 in MEF2-Dependent Synapse Elimination

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. [Display omitted] •Dendritic mGluR5 activity is required for MEF2-induced synapse elimination•mGluR5 mediates dendritic translation of MEF2-induced Arc mRNA•Arc is necessary, but not sufficient, for MEF2-dependent synapse elimination Experience-dependent refinement of neural connectivity occurs through activation of somatically localized transcription factors. Whether local regulation of new transcripts at the synapse is required for synapse refinement is unclear. Huber and colleagues demonstrate that synapse elimination induced by an activity-dependent transcription factor, myocyte enhancer factor 2 (MEF2), requires dendritic mGluR5-mediated translation of a target gene, activity-regulated cytoskeletal-associated protein (Arc). Arc is necessary, but not sufficient, for synapse elimination. Thus, local synaptic activity regulates transcription factor-induced changes in synaptic function.