Inositol-1,4,5-trisphosphate-mediated rescue of cerebellar long-term depression in subtype 1 metabotropic glutamate receptor mutant mouse

Neuroscience. 1999;92(1):1-6. doi: 10.1016/s0306-4522(99)00136-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / physiology
  • Cerebellum / physiology*
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Inositol 1,4,5-Trisphosphate / analogs & derivatives
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol 1,4,5-Trisphosphate / physiology*
  • Long-Term Potentiation / drug effects
  • Long-Term Potentiation / physiology*
  • Mice
  • Mice, Knockout / genetics
  • Photolysis
  • Protein Kinase C / antagonists & inhibitors
  • Purkinje Cells / metabolism
  • Receptors, Metabotropic Glutamate / deficiency*
  • Receptors, Metabotropic Glutamate / genetics
  • Signal Transduction / physiology


  • Enzyme Inhibitors
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • inositol 1,4,5-trisphosphate 1-(2-nitrophenyl)ethyl ester
  • Inositol 1,4,5-Trisphosphate
  • Protein Kinase C
  • Calcium