Altered Neuronal Excitability in Cerebellar Granule Cells of Mice Lacking Calretinin

David Gall, Céline Roussel, Isabella Susa, Egidio D'Angelo, Paola Rossi, Bertrand Bearzatto, Marie Christine Galas, David Blum, Stéphane Schurmans, Serge N. Schiffmann

Research output: Contribution to journalArticlepeer-review

Abstract

Calcium-binding proteins such as calretinin are abundantly expressed in distinctive patterns in the CNS, but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells, which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin-deficient mice exhibit dramatic alterations in motor coordination and Purkinje cell firing recorded in vivo through unknown mechanisms. In the present study, we used patch-clamp recording techniques in acute slice preparation to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin-deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0. 15 mM of the exogenous fast-calcium buffer BAPTA is infused in the cytosol to restore the calcium-buffering capacity. A proposed mathematical model demonstrates that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium-buffering capacity resulting from the absence of calretinin. This result suggests that calcium-binding proteins modulate intrinsic neuronal excitability and may therefore play a role in information processing in the CNS.

Original languageEnglish
Pages (from-to)9320-9327
Number of pages8
JournalJournal of Neuroscience
Volume23
Issue number28
Publication statusPublished - Oct 15 2003

Keywords

  • Calcium
  • Calcium-binding protein
  • Calretinin
  • Cerebellar granule cell
  • Excitability
  • Mathematical model

ASJC Scopus subject areas

  • Neuroscience(all)

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