title: Impaired motor coordination and Purkinje cell excitability in mice lacking calretinin.
abstract: 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 ([Ca2+]i). Ca2+ 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 Ca2+ homeostasis in Cr-/- Purkinje cells was supported by the high Ca2+-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.
authors.affiliation: Brain Research Unit CP601, Université Libre de Bruxelles, 1070 Brussels, Belgium. sschiffm@ulb.ac.be
authors.forename: S N
authors.initials: SN
authors.lastname: Schiffmann
authors.forename: G
authors.initials: G
authors.lastname: Cheron
authors.forename: A
authors.initials: A
authors.lastname: Lohof
authors.forename: P
authors.initials: P
authors.lastname: d'Alcantara
authors.forename: M
authors.initials: M
authors.lastname: Meyer
authors.forename: M
authors.initials: M
authors.lastname: Parmentier
authors.forename: S
authors.initials: S
authors.lastname: Schurmans
mesh_terms: D000375:Aging; D000818:Animals; D064032:Calbindin 2; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000502:physiology; D009473:Neuronal Plasticity; D011689:Purkinje Cells / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000502:physiology*
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G