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 longterm depression requires t he activation of subtype 1 metabotropic glutamate receptors, since long-ter m depression is impaired in subtype 1 metabotropic glutamate receptor (mGlu R1) knockout mice.(1,4) In order to better define the role of mGluR1-activa ted signal transduction pathways, we attempted to rescue cerebellar long-te rm depression in mGluR1 knockout mice by direct activation of subsequent in tracellular cascades. The present results demonstrate that the inositol-1,4 ,5-trisphosphate signal transduction pathway remains functional in mGluR1 k nockout mice, that calcium release from internal stores evoked by the combi ned photolytic release of inositol-1,4,5-trisphosphate/pairing protocol is sufficient to rescue long-term depression in these mutants, and that this l ong-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 develop mental abnormalities, but is directly due to mGluR1 gene inactivation. (C) 1999 IBRO, Published by Elsevier Science Ltd.