Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene

Matti S. Airaksinen, Jens Eilers, Olga Garaschuk, Hans Thoenen, Arthur Konnerth, Michael Meyer

Research output: Contribution to journalArticlepeer-review

359 Scopus citations

Abstract

Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear. To investigate the physiological role of a major endogenous calcium-binding protein, calbindin D28k (calbindin) in vivo, we have generated calbindin null mutant mice by gent targeting. Surprisingly, calbindin deficiency does nut affect general parameters of development and behavior or the structure of the nervous system at the light microscopic level. Null mutants are, however, severely impaired in tests of motor coordination, suggesting functional deficits in cerebellar pathways. Purkinje neurons, the only efferent of the cerebellar cortex, and inferior olive neurons, the source of the climbing fiber afferent, have previously been shown to express calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging of Purkinje cells in cerebellar slices revealed marked changes of synaptically evoked postsynaptic calcium transients. Their fast, but not their slow, decay component had larger amplitudes in null mutant than in wild-type mice. We conclude that endogenous calbindin is of crucial importance fur integrated nervous system function.

Original languageEnglish
Pages (from-to)1488-1493
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number4
DOIs
StatePublished - 18 Feb 1997
Externally publishedYes

Keywords

  • calcium imaging
  • calcium-binding protein
  • cerebellar Purkinje neurons
  • motor coordination
  • synaptically evoked calcium transients

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