Differential roles for group 1 mGluR subtypes in induction and expression of chemically induced hippocampal long-term depression

J Neurophysiol. 2006 Apr;95(4):2427-38. doi: 10.1152/jn.00383.2005. Epub 2006 Jan 18.

Abstract

Although metabotropic glutamate receptors (mGluRs) mGluR1 and mGluR5 are often found to have similar functions, there is considerable evidence that the two receptors also serve distinct functions in neurons. In hippocampal area CA1, mGluR5 has been most strongly implicated in long-term synaptic depression (LTD), whereas mGluR1 has been thought to have little or no role. Here we show that simultaneous pharmacological blockade of mGluR1 and mGluR5 is required to block induction of LTD by the group 1 mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG). Blockade of mGluR1 or mGluR5 alone has no effect on LTD induction, suggesting that activation of either receptor can fully induce LTD. Consistent with this conclusion, mGluR1 and mGluR5 both contribute to activation of extracellular signal-regulated kinase (ERK), which has previously been shown to be required for LTD induction. In contrast, selective blockade of mGluR1, but not mGluR5, reduces the expression of LTD and the associated decreases in AMPA surface expression. LTD is also reduced in mGluR1 knockout mice confirming the involvement of mGluR1. This shows a novel role for mGluR1 in long-term synaptic plasticity in CA1 pyramidal neurons. In contrast to DHPG-induced LTD, synaptically induced LTD with paired-pulse low-frequency stimulation persists in the pharmacological blockade of group 1 mGluRs and in mGluR1 or mGluR5 knockout mice. This suggests different receptors and/or upstream mechanisms for chemically and synaptically induced LTD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Amino Acids / pharmacology
  • Animals
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Hippocampus / chemistry
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Long-Term Synaptic Depression*
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Mice, Knockout
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / chemistry
  • Neurons / drug effects
  • Neurons / physiology
  • Neurotransmitter Agents / physiology
  • Phosphorylation
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Metabotropic Glutamate 5
  • Receptors, AMPA / analysis
  • Receptors, AMPA / physiology
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / classification
  • Receptors, Metabotropic Glutamate / physiology*
  • Synapses / drug effects
  • Synapses / physiology
  • Xanthenes / pharmacology

Substances

  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • Grm5 protein, mouse
  • Grm5 protein, rat
  • LY 341495
  • Neurotransmitter Agents
  • Pyridines
  • Receptor, Metabotropic Glutamate 5
  • Receptors, AMPA
  • Receptors, Metabotropic Glutamate
  • Xanthenes
  • metabotropic glutamate receptor type 1
  • Methoxyhydroxyphenylglycol
  • 6-methyl-2-(phenylethynyl)pyridine
  • Extracellular Signal-Regulated MAP Kinases
  • 3,4-dihydroxyphenylglycol