Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate Receptors

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 mGluRl-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 antischizophrenia drugs that disrupt Homer-containing protein link.

Original languageEnglish
Pages (from-to)9840-9855
Number of pages16
JournalJOURNAL OF NEUROSCIENCE
Volume38
Issue number46
DOIs
Publication statusPublished - 14 Nov 2018

Keywords

  • cerebellar granule cells
  • dentate gyms granule cells
  • Homer protein
  • inter-receptor crosstalk
  • metabotropic glutamate receptors
  • NMDA receptors
  • CEREBELLAR GRANULE CELLS
  • RAT HIPPOCAMPAL SLICES
  • LONG-TERM POTENTIATION
  • SYNAPTIC PLASTICITY
  • DENTATE GYRUS
  • SCHIZOPHRENIA
  • NEURONS
  • ACTIVATION
  • PROTEINS
  • HOMER

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