Impaired motor coordination and Purkinje cell excitability in mice lackingcalretinin

In the cerebellum, the parallel fiber-Purkinje cell synapse can undergo lon g-term synaptic plasticity suggested to underlie motor learning and resulti ng from variations in intracellular calcium concentration ([Ca2+](i)). Ca2 binding proteins are enriched in the cerebellum but their role in informat ion processing is not clear. Here, we show that mice deficient in calretini n (Cr-/-) are impaired in tests of motor coordination. An impairment in Ca2 + homeostasis in Cr-/- Purkinje cells was supported by the high Ca2+- satur ation of calbindin-D28k in these cells. The firing behavior of Purkinje cel ls is severely affected in Cr-/- alert mice, with alterations of simple spi ke firing rate, complex spike duration, and simple spike pause. In contrast , in slices, transmission at parallel fiber- or climbing fiber-Purkinje cel l synapses is unaltered, indicating that marked modifications of the firing behavior in vivo can be undetectable in slice. Thus, these results show th at calretinin plays a major role at the network level in cerebellar physiol ogy.