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PMID: 14568994 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 163 ·No. 2 ·2003-10-27 ·Pages 295-302

Feil R, Hartmann J, Luo C, Wolfsgruber W, Schilling K, Feil S, Barski JJ, Meyer M, Konnerth A, De Zeeuw CI, Hofmann F

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.

MeSH Terms
Adaptation, Physiological/genetics Animals Cerebellum/cytology,metabolism Cyclic GMP-Dependent Protein Kinase Type I Cyclic GMP-Dependent Protein Kinases/deficiency,genetics,metabolism Learning/physiology Long-Term Potentiation/physiology Mice Mice, Knockout Mice, Transgenic Mutation Purkinje Cells/cytology,enzymology,metabolism Reflex, Vestibulo-Ocular/genetics Synapses/physiology Synaptic Transmission/physiology
Chemicals
Cyclic GMP-Dependent Protein Kinase Type I Cyclic GMP-Dependent Protein Kinases Prkg1 protein, mouse
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Feil Robert
Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Str. 29, D-80802 München, Germany.
Hartmann Jana
Luo Chongde
Wolfsgruber Wiebke
Schilling Karl
Feil Susanne
Barski Jaroslaw J
Meyer Michael
Konnerth Arthur
De Zeeuw Chris I
Hofmann Franz
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200306148
Published
2003-10-27
Epub
2003-00-20
Pages
295-302
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2173527
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200306148 PMC Full Text View journal details
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