Long-term depression induced by postsynaptic group II metabotropic glutamate receptors linked to phospholipase C and intracellular calcium rises in rat prefrontal cortex.
We have previously shown (Otani et al., 1999b) that bath application of (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV), the agonist of group II metabotropic glutamate receptors (mGluRs), induces postsynaptic Ca2+-dependent long-term depression (LTD) of layer I-II to layer V pyramidal neuron glutamatergic synapses of rat medial prefrontal cortex. In the present study, we examined detailed mechanisms of this DCG IV-induced LTD. First, the group II mGluR antagonist (RS)-alpha-methylserine-O-phosphate monophenyl ester blocked DCG IV-induced LTD, and another group II agonist (2S,3S,4S)-CCG/(2S,1'S,2'S)-2-(carboxycyclopropyl)glycine-induced LTD, suggesting that LTD is indeed mediated by the activation of group II mGluRs. Second, DCG IV-induced LTD was blocked by the NMDA receptor antagonist AP-5, whereas DCG IV did not potentiate NMDA receptor-mediated synaptic responses. Interruption of single test stimuli during DCG IV application blocked DCG IV-induced LTD. These results suggest that small NMDA receptor-mediated responses evoked by single synaptic stimuli contribute to DCG IV-induced LTD. Third, DCG IV-induced LTD was blocked or reduced by the following drugs: phospholipase C inhibitor U-73122 (bath-applied or postsynaptically injected), postsynaptically injected IP3 receptor blocker heparin, phospholipase D-linked mGluR blocker PCCG-13, PKC inhibitor RO318220, postsynaptically injected PKC inhibitor PKC(19-36), and PKA inhibitor KT-5720. Fourth, fluorescent Ca2+ analysis techniques revealed that DCG IV increases Ca2+ concentration in prefrontal layer V pyramidal neurons. These Ca2+ rises and the LTD were both blocked by postsynaptic heparin in the same cells. Taken together, these results suggest that postsynaptic group II mGluRs, linked to phospholipase C and probably also phospholipase D, induce LTD through postsynaptic PKC activation and IP3 receptor-mediated postsynaptic increases of Ca2+ concentration.
Otani
S
S
Neurobiologie des Processus Adaptatifs, Université de Paris VI, 75005 Paris, France. satoru.otani@snv.jussieu.fr
Daniel
H
H
Takita
M
M
Crépel
F
F
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D003521:Cyclopropanes / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013995:Time; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D015220:Calcium Channels; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D006493:Heparin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D; D002118:Calcium; D005998:Glycine