Induction of LTD by activation of group I mGluR in the dentate gyrus in vitro

Neuropharmacology. 1999 Oct;38(10):1597-606. doi: 10.1016/s0028-3908(99)00093-3.


The ability of activation of group I metabotropic glutamate receptors (mGluR) to induce long-term depression (LTD) was investigated in the medial perforant path of the dentate gyrus in vitro. Application of the group I agonists (RS)-3,5-dihydroxyphenylglycine (DHPG) and (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), and also the partial agonist (S)-(+)-2-(3'-Carboxybicyclo[1.1.1]pentyl)-glycine (UPF 596), induced LTD of the field EPSP. The induction of LTD is likely to be mediated via mGluR5 since CHPG and UPF 596 are selective agonists/partial agonists at that receptor. Further evidence for the involvement of group I mGluR in LTD induction was the finding, that the DHPG and low frequency stimulation induced LTD were inhibited by the group I mGluR antagonist [CRS]-1-aminoindan-1,5-dicarboxylic acid (AIDA). Investigation of the intracellular mechanisms underlying the induction of the group I mGluR-mediated LTD showed an inhibition of the LTD by the protein kinase C (PKC) inhibitor bisindolylmaleimide I and the protein tyrosine kinase inhibitor lavendustin A, but not the PKA inhibitor H89. These studies demonstrate that DHPG-induced LTD can be induced by the activation of mGluR5 followed by intracellular stimulation of PKC and tyrosine kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / physiology*
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • In Vitro Techniques
  • Indans / pharmacology
  • Indoles / pharmacology
  • Isoquinolines / pharmacology
  • Maleimides / pharmacology
  • Methoxyhydroxyphenylglycol / analogs & derivatives*
  • Methoxyhydroxyphenylglycol / pharmacology
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Phenols / pharmacology
  • Phenylacetates / pharmacology*
  • Protein Kinase C / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Sulfonamides*


  • 1-aminoindan-1,5-dicarboxylic acid
  • 2-chloro-5-hydroxyphenylglycine
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Indans
  • Indoles
  • Isoquinolines
  • Maleimides
  • Phenols
  • Phenylacetates
  • Receptors, Metabotropic Glutamate
  • Sulfonamides
  • lavendustin A
  • Methoxyhydroxyphenylglycol
  • Protein-Tyrosine Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • bisindolylmaleimide I
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • Glycine
  • 3,4-dihydroxyphenylglycol