A slow excitatory postsynaptic current mediated by a novel metabotropic glutamate receptor in CA1 pyramidal neurons

Neuropharmacology. 2017 Mar 15:115:4-9. doi: 10.1016/j.neuropharm.2016.08.028. Epub 2016 Aug 25.

Abstract

Slow excitatory postsynaptic currents (EPSCs) mediated by metabotropic glutamate receptors (mGlu receptors) have been reported in several neuronal subtypes, but their presence in hippocampal pyramidal neurons remains elusive. Here we find that in CA1 pyramidal neurons a slow EPSC is induced by repetitive stimulation while ionotropic glutamate receptors and glutamate-uptake are blocked whereas it is absent in the VGLUT1 knockout mouse in which presynaptic glutamate is lost, suggesting the slow EPSC is mediated by glutamate activating mGlu receptors. However, it is not inhibited by known mGlu receptor antagonists. These findings suggest that this slow EPSC is mediated by a novel mGlu receptor, and that it may be involved in neurological diseases associated with abnormal high-concentration of extracellular glutamate. This article is part of the Special Issue entitled 'Metabotropic Glutamate Receptors, 5 years on'.

Keywords: CA1 neuron; Glutamate uptake; Slow EPSC; TBOA; mGlu receptor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • Female
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Male
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Mice, Knockout
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Vesicular Glutamate Transport Protein 1 / antagonists & inhibitors
  • Vesicular Glutamate Transport Protein 1 / deficiency*

Substances

  • Benzoates
  • Excitatory Amino Acid Antagonists
  • Receptors, Metabotropic Glutamate
  • Slc17a7 protein, mouse
  • Vesicular Glutamate Transport Protein 1
  • alpha-methyl-4-carboxyphenylglycine
  • Methoxyhydroxyphenylglycol
  • Glycine
  • 3,4-dihydroxyphenylglycol