Impaired motor coordination and Purkinje cell excitability in mice lacking calretinin

In the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium concentration ([Ca(2+)](i)). Ca(2+) binding proteins are enriched in the cerebellum, but their role in information processing is not clear. Here, we show that mice deficient in calretinin (Cr(−/−)) are impaired in tests of motor coordination. An impairment in Ca(2+) homeostasis in Cr(−/−) Purkinje cells was supported by the high Ca(2+)-saturation of calbindin-D28k in these cells. The firing behavior of Purkinje cells is severely affected in Cr(−/−) alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause. In contrast, in slices, transmission at parallel fiber- or climbing fiber-Purkinje cell synapses is unaltered, indicating that marked modifications of the firing behavior in vivo can be undetectable in slice. Thus, these results show that calretinin plays a major role at the network level in cerebellar physiology