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 (mGlu R) to induce long-term depression (LTD) was investigated in the medial perf orant path of the dentate gyrus in vitro. Application of the group I agonis ts (RS)-3,5-dihydroxyphenylglycine (DHPG) and (RS)-2-chloro-5-hydroxyphenyl glycine (CHPG), and also the partial agonist (S)-(+)-2-(3'-Carboxy bicyclo[ 1.1.1]pentyl)-glycine (UPF 596), induced LTD of the field EPSP. The inducti on of LTD is likely to be mediated via mGluR5 since CHPG and UPF 596 are se lective agonists/partial agonists at that receptor. Further evidence for th e involvement of group I mGluR in LTD induction was the finding that the DH PG and low frequency stimulation induced LTD were inhibited by the group I mGluR antagonist [CRS]-1-aminoindan-1,5-dicarboxylic acid (AIDA). Investiga tion 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 inh ibitor lavendustin A, but not the PKA inhibitor H89. These studies demonstr ate that DHPG-induced LTD can be induced by the activation of mGluR5 follow ed by intracellular stimulation of PKC and tyrosine kinase. (C) 1999 Elsevi er Science Ltd. All rights reserved.