Elsevier

Neuropharmacology

Volume 36, Issues 11–12, November–December 1997, Pages 1517-1532
Neuropharmacology

The group I mGlu receptor agonist DHPG induces a novel form of LTD in the CA1 region of the hippocampus

https://doi.org/10.1016/S0028-3908(97)00181-0Get rights and content

Abstract

The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) (100 μM, 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 GABAA receptor antagonist picrotoxin (29 ± 2%). The N-methyl-D-aspartate (NMDA) receptor antagonist AP5 (100 μM) 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 μM. Neither agonists specific for group II (100 nM DCG-IV or 1 μM LY354740) or group III (10 μM l-AP4) mGlu receptors or a combined group I and II agonist (30–100 μM (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.

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