Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of cGMP-dependent protein kinase I

Robert Feil, Jana Hartmann, Chongde Luo, Wiebke Wolfsgruber, Karl Schilling, Susanne Feil, Jaroslaw J. Barski, Michael Meyer, Arthur Konnerth, Chris I. De Zeeuw, Franz Hofmann

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

The molecular basis for cerebellar plasticity and motor learning remains controversial. Cerebellar Purkinje cells (PCs) contain a high concentration of cGMP-dependent protein kinase type I (cGKI). To investigate the function of cGKI in long-term depression (LTD) and cerebellar learning, we have generated conditional knockout mice lacking cGKI selectively in PCs. These cGKI mutants had a normal cerebellar morphology and intact synaptic calcium signaling, but strongly reduced LTD. Interestingly, no defects in general behavior and motor performance could be detected in the LTD-deficient mice, but the mutants exhibited an impaired adaptation of the vestibulo-ocular reflex (VOR). These results indicate that cGKI in PCs is dispensable for general motor coordination, but that it is required for cerebellar LTD and specific forms of motor learning, namely the adaptation of the VOR.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - 27 Oct 2003
Externally publishedYes

Keywords

  • CGMP kinase
  • Cre recombinase
  • Intracellular signaling
  • Learning
  • Synaptic plasticity

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