Roles for Arc in metabotropic glutamate receptor-dependent LTD and synapse elimination: Implications in health and disease

Research output: Contribution to journalReview article

13 Scopus citations

Abstract

The Arc gene is robustly transcribed in specific neural ensembles in response to experience-driven activity. Upon induction, Arc mRNA is transported to dendrites, where it can be rapidly and locally translated by activation of metabotropic glutamate receptors (mGluR1/5). mGluR-induced dendritic synthesis of Arc is implicated in weakening or elimination of excitatory synapses by triggering endocytosis of postsynaptic AMPARs in both hippocampal CA1 and cerebellar Purkinje neurons. Importantly, CA1 neurons with experience-induced Arc mRNA are susceptible, or primed for mGluR-induced long-term synaptic depression (mGluR-LTD). Here we review mechanisms and function of Arc in mGluR-LTD and synapse elimination and propose roles for these forms of plasticity in Arc-dependent formation of sparse neural representations of learned experience. We also discuss accumulating evidence linking dysregulation of Arc and mGluR-LTD in human cognitive disorders such as intellectual disability, autism and Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)51-62
Number of pages12
JournalSeminars in Cell and Developmental Biology
Volume77
DOIs
StatePublished - May 2018

Keywords

  • Arc/Arg3.1
  • Dynamin
  • Long-term synaptic depression
  • Synapse elimination
  • mGluR5

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Roles for Arc in metabotropic glutamate receptor-dependent LTD and synapse elimination: Implications in health and disease'. Together they form a unique fingerprint.

  • Cite this