The molecular mechanisms underlying learning and memory are conserved between primitive and higher organized organisms. Memory formation requires plasticity between synaptic connections, and Ca2+ serves as an essential second messenger in the regulation of this plasticity. Calcium-calmodulin dependent protein kinase II (CaMKII) detects the amplitude and frequency of the Ca2+ signal, and transforms this transient signal into a graded, long-lasting Ca2+ independent signal. Activated CaMKII phosphorylates itself and various other proteins, which eventually leads to enhancement of synaptic efficacy. Because of these unique properties, it is not surprising that the CaMKII knock- out mouse was the first mouse to be studied in the field of Neuroscience. Since then, its role in hippocampal plasticity and hippocampal learning and memory has been intensely studied. These studies were subsequently replicated for cortical areas, for which the molecular mechanisms are very similar as the hippocampus. The molecular mechanisms underlying cerebellar motor learning are markedly different compared to excitatory neurons of the forebrain. Influx of high amounts of calcium into cerebellar Purkinje cells results in synaptic weakening rather than strengthening. In this thesis we explored the possibility that CaMKII might be involved in this weakening process and in cerebellar motor learning.