Induction of LTD by activation of group I mGluR in the dentate gyrus in vitro.
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.
Camodeca
N
N
Department of Physiology, Trinity College, Dublin, Ireland.
Breakwell
N A
NA
Rowan
M J
MJ
Anwyl
R
R
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013449:Sulfonamides
C095756:1-aminoindan-1,5-dicarboxylic acid; C107349:2-chloro-5-hydroxyphenylglycine; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007189:Indans; D007211:Indoles; D007546:Isoquinolines; D008301:Maleimides; D010636:Phenols; D010648:Phenylacetates; D018094:Receptors, Metabotropic Glutamate; D013449:Sulfonamides; C062898:lavendustin A; D008734:Methoxyhydroxyphenylglycol; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005998:Glycine; C010117:3,4-dihydroxyphenylglycol