Metabotropic glutamate receptors induce a form of LTP controlled by translation and arc signaling in the hippocampus

Hui Wang, Alvaro O. Ardiles, Sunggu Yang, Trinh Tran, Rafael Posada-Duque, Gonzalo Valdivia, Min Baek, Yang An Chuang, Adrian G. Palacios, Michela Gallagher, Paul Worley, Alfredo Kirkwood

Research output: Contribution to journalArticlepeer-review

Abstract

Activity-dependent bidirectional modifications of excitatory synaptic strength are essential for learning and storage on new memories. Research on bidirectional synaptic plasticity has largely focused on long-term potentiation (LTP) and long-term depression (LTD) mechanisms that rely on the activation ofNMDAreceptors. In principle, metabotropic glutamate receptors (mGluRs) are also suitable to convert synaptic activity into intracellular signals for synaptic modification. Indeed, dysfunction of a form of LTD that depends on Type I mGluRs (mGluR-LTD), but not NMDARs, has been implicated in learning deficits in aging and mouse models of several neurological conditions, including Fragile X syndrome and Alzheimer’s disease. To determine whether mGluR activation can also induce LTP in the absence of NMDAR activation, we examined in hippocampal slices from rats and mice, an NMDAR-independent form of LTP previously characterized as dependent on voltage-gated Ca2+ channels. We found that this form of LTP requires activation of Type I mGluRs and, like mGluR-LTD but unlike NMDAR-dependent plasticity, depends crucially on protein synthesis controlled by fragile X mental retardation protein and on Arc signaling. Based on these observations, we propose the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs.

Original languageEnglish (US)
Pages (from-to)1723-1729
Number of pages7
JournalJournal of Neuroscience
Volume36
Issue number5
DOIs
StatePublished - Feb 3 2016

Keywords

  • Arc
  • Bidirectional
  • Metabotropic glutamate receptors
  • Protein synthesis
  • Synaptic plasticity
  • Translation

ASJC Scopus subject areas

  • Neuroscience(all)

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