Group II mGluR-induced long term depression in the dentate gyrus in vivo is NMDA receptor-independent and does not require protein synthesis.
Long term depression (LTD) can be induced by low frequency stimulation (LFS) as well as by agonist activation of neurotransmitter receptors. Group II metabotropic glutamate receptors (mGluRs) play an essential role in the regulation of electrically-induced LTD in the hippocampus in vivo: LTD is inhibited by antagonists, and enhanced by agonists of group II mGluRs. Here we investigated induction of LTD by activation of group II mGluRs as well as the cellular mechanisms which might mediate group II mGluR-induced LTD. Rats were implanted with electrodes to enable chronic measurement of evoked potentials from medial perforant path-dentate gyrus synapses. Drug application was made through a cannula implanted into the ipsilateral cerebral ventricle. LTD could be induced by agonist activation of either group II mGluRs, or the group II mGluR subtype, mGluR3. Both, group II mGluR-induced LTD and mGluR3-induced LTD were not abolished by mRNA/protein synthesis inhibition. Furthermore, mGluR3-induced LTD was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated calcium channel blockers. Our data suggest that sole activation of group II mGluRs can mediate LTD in vivo. Intriguingly, this form of LTD is not dependent on protein synthesis or activation of NMDA receptors.
Pöschel
Beatrice
B
Learning and Memory Research, Medical Faculty, Ruhr University Bochum, Germany.
Manahan-Vaughan
Denise
D
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004151:Dipeptides / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004151:Dipeptides; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D011500:Protein Synthesis Inhibitors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C108822:metabotropic glutamate receptor 2; C078245:4-carboxy-3-hydroxyphenylglycine; C027172:isospaglumic acid; D000841:Anisomycin; D015763:2-Amino-5-phosphonovalerate; D014700:Verapamil; D005998:Glycine