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

The group I specific metabotropic glutamate (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) (100 mu M, 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 mu M) 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 mu M. Neither agonists specific for group II (100 nM DCG-IV or 1 mu M LY354740) or group III (10 mu M L-AP4) mGlu receptors or a combined group I and II agonist (30-100 mu M (1S,3R)-ACPD) induced LTD. However, an agonist (1 mM CHPG) which activates mGlu(5) but not mGlu(1) 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 mGlu(5)) can induce LTD and that this mGlu receptor-mediated LTD may, or may not, require activation of NMDA receptors, depending on the experimental conditions. (C) 1998 Elsevier Science Ltd. All rights reserved.