Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate Receptors

Nathanael O'Neill, Catherine McLaughlin, Noboru Komiyama, Sergiy Sylantyev

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

A recently reported rapid potentiation of NMDA receptors by Group I metabotropic glutamate receptors (mGluRIs) via a Homer protein link is distinct from the classical, relatively slow inhibitory G-protein-associated signaling triggered by mGluRI activation. The relationship between these two mechanisms remains unknown. Here, we focused on the mGluRI-dependent modulation of NMDAR response in hippocampal dentate gyrus granule cells and cerebellar granule cells of C57BL6-J mice and found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. At a shorter time interval (units of millisecond), the Homer-mediated signal from mGluRIs prevails, causing upregulation of NMDAR function, in both dentate gyrus granule cells and cerebellar granule cells. Our results shed light on the possible mechanisms of anti-schizophrenia drugs that disrupt Homer-containing protein link.

Original languageEnglish
Pages (from-to)9840-9855
Number of pages16
JournalJournal of Neuroscience
Volume38
Issue number46
Early online date3 Oct 2018
DOIs
Publication statusPublished - 14 Nov 2018

Keywords

  • cerebellar granule cells
  • dentate gyrus granule cells
  • Homer protein
  • inter-receptor
  • cross talk
  • metabotropic glutamate receptors
  • NMDA receptors

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