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 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.
Palmer
M J
MJ
Department of Anatomy, School of Medical Sciences, University of Bristol, UK. m.j.palmer@bristol.ac.uk
Irving
A J
AJ
Seabrook
G R
GR
Jane
D E
DE
Collingridge
G L
GL
D000818:Animals; D003864:Depression, Chemical; D004558:Electric Stimulation; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D058785:GABA-A Receptor Agonists; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D009473:Neuronal Plasticity / Q000187:drug effects*; D051381:Rats; D012118:Resorcinols / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D018690:Excitatory Amino Acid Agonists; D058785:GABA-A Receptor Agonists; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine