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 ([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.
Schiffmann
S N
SN
Brain Research Unit CP601, Université Libre de Bruxelles, 1070 Brussels, Belgium. sschiffm@ulb.ac.be
Cheron
G
G
Lohof
A
A
d'Alcantara
P
P
Meyer
M
M
Parmentier
M
M
Schurmans
S
S
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*
C576511:Calb2 protein, mouse; D064032:Calbindin 2; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G