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© The Rockefeller University Press, 0021-9525/2003/10/295 $8.00
The Journal of Cell Biology, Volume 163, Number 2, 295-302

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

¹ Institut für Pharmakologie und Toxikologie, Technische Universität, 80802 München, Germany
² Physiologisches Institut, Ludwig-Maximilians-Universität, 80336 München, Germany
³ Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, Netherlands
⁴ Anatomisches Institut, Anatomie und Zellbiologie, Rheinische Friedrich-Wilhelms-Universität Bonn, 53115 Bonn, Germany
⁵ Institute of Ophthalmology, Department of Molecular Genetics, University College London, London EC1V9EL, UK

Address correspondence to Franz Hofmann, Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Str. 29, D-80802 München, Germany. Tel.: 49-89-4140-3260. Fax: 49-89-4140-3261. email: Hofmann{at}ipt.med.tu-muenchen.de

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.

Key Words: cGMP kinase; Cre recombinase; intracellular signaling; synaptic plasticity; learning

Abbreviations used in this paper: cGKI, cGMP-dependent protein kinase type I; DSCT, delayed synaptic Ca²⁺ transient; EPSC, excitatory postsynaptic current; ESCT, early synaptic Ca²⁺ transient; LTD, long-term depression; OKR, optokinetic reflex; PC, Purkinje cell; VOR, vestibulo-ocular reflex; VVOR, VOR in the light.

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