The Group I mGlu Receptor Agonist DHPG Induces a Novel Form of LTD in the CA1 Region of the Hippocampus

Neuropharmacology. Nov-Dec 1997;36(11-12):1517-32. doi: 10.1016/s0028-3908(97)00181-0.

Abstract

The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) (100 microM, 10 min) induced long-term depression (LTD) of synaptic transmission in the CA1 region of adult rat hippocampal slices, measured using a grease-gap recording technique. In "normal" (1 mM Mg2+-containing) medium, LTD (measured 30 min after washout of DHPG) was small (13+/-3%), but LTD was enhanced if DHPG was applied when the tissue was made hyperexcitable, either by omitting Mg2+ from the perfusate (35+/-3%) or by adding the GABA(A) receptor antagonist picrotoxin (29+/-2%). The N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (100 microM) substantially reduced the generation of DHPG-induced LTD in Mg2+-free medium, but had little effect on LTD induced in the presence of picrotoxin. In Mg2+-free medium, the threshold concentration of DHPG required to induce LTD was between 1 and 3 microM. Neither agonists specific for group II (100 nM DCG-IV or 1 microM LY354740) or group III (10 microM L-AP4) mGlu receptors or a combined group I and II agonist (30-100 microM (1S,3R)-ACPD) induced LTD. However, an agonist (1 mM CHPG) which activates mGlu5 but not mGlu1 receptors did induce LTD. Surprisingly, DHPG-induced LTD was reversed by mGlu receptor antagonists, applied hours after washout of DHPG. DHPG-induced LTD did not occlude with LTD induced by synaptic activation (1200 stimuli delivered at 2 Hz), in Mg2+-free medium. These data show that activation of group I mGlu receptors (probably mGlu5) can induce LTD and that this mGlu receptor-mediated LTD may, or may not, require activation of NMDA receptors, depending on the experimental conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Depression, Chemical
  • Electric Stimulation
  • Electrophysiology
  • Excitatory Amino Acid Agonists / pharmacology*
  • Female
  • GABA-A Receptor Agonists
  • Glycine / analogs & derivatives*
  • Glycine / pharmacology
  • Hippocampus / drug effects*
  • In Vitro Techniques
  • Neuronal Plasticity / drug effects*
  • Rats
  • Resorcinols / pharmacology*
  • Synaptic Transmission / drug effects

Substances

  • Excitatory Amino Acid Agonists
  • GABA-A Receptor Agonists
  • Resorcinols
  • 3,5-dihydroxyphenylglycine
  • Glycine