Inositol-1,4,5-trisphosphate-mediated rescue of cerebellar long-term depression in subtype 1 metabotropic glutamate receptor mutant mouse.
Recent reports have outlined that cerebellar long-term depression requires the activation of subtype 1 metabotropic glutamate receptors, since long-term depression is impaired in subtype 1 metabotropic glutamate receptor (mGluR1) knockout mice. In order to better define the role of mGluR1-activated signal transduction pathways, we attempted to rescue cerebellar long-term depression in mGluR1 knockout mice by direct activation of subsequent intracellular cascades. The present results demonstrate that the inositol-1,4,5-trisphosphate signal transduction pathway remains functional in mGluR1 knockout mice, that calcium release from internal stores evoked by the combined photolytic release of inositol- 1,4,5-trisphosphate/pairing protocol is sufficient to rescue long-term depression in these mutants, and that this long-term depression is sensitive to a protein kinase C inhibitor. Therefore, our results provide compelling evidence that the impairment of long-term depression observed in mGluR1 knockout mice is not a consequence of developmental abnormalities, but is directly due to mGluR1 gene inactivation.
Institut des Neurosciences, CNRS-Université Paris VI, France.
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H
Daniel
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C
Levenes
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L
Fagni
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Conquet
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Bockaert
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Crepel
D000818:Animals; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D015544:Inositol 1,4,5-Trisphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010782:Photolysis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011689:Purkinje Cells / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology
D004791:Enzyme Inhibitors; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C061868:inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D002118:Calcium