Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of cGMP-dependent protein kinase I.
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.
Institut für Pharmakologie und Toxikologie, Technische Universität, Biedersteiner Str. 29, D-80802 München, Germany.
Robert
R
Feil
Jana
J
Hartmann
Chongde
C
Luo
Wiebke
W
Wolfsgruber
Karl
K
Schilling
Susanne
S
Feil
Jaroslaw J
JJ
Barski
Michael
M
Meyer
Arthur
A
Konnerth
Chris I
CI
De Zeeuw
Franz
F
Hofmann
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D011689:Purkinje Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse