In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model

Polina A. Egorova, Olga A. Zakharova, Olga L. Vlasova, Ilya B. Bezprozvanny

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Cerebellar Purkinje cells (PCs) are primarily affected in many spinocerebellar ataxias (SCA). In this study we investigated functional activity of PCs in transgenic mouse model of SCA2, a polyglutamine neurodegenerative hereditary disorder. In our studies we used extracellular single-unit recording method to compare spontaneous activity of PCs in agematched wild-type mice and SCA2-58Q transgenic mice. We discovered that the fraction of PCs with bursting and an irregular pattern of spontaneous activity dramatically increases in aged SCA2-58Q mice compared with wild-type littermates. Small-conductance calciumactivated potassium (SK) channels play an important role in determining firing rate of PCs. Indeed, we demonstrated that intraperitoneal (IP) injection of SK channel inhibitor NS8593 induces an irregular pattern of PC activity in wild-type mice. Furthermore, we demonstrated that IP injection of SK channel-positive modulator chlorzoxazone (CHZ) decreases spontaneous firing rate of cerebellar PCs. Finally, we have shown that IP injections with CHZ normalize firing activity of cerebellar PCs from aging SCA2-58Q mice. We propose that alterations in PC firing patterns is one of potential causes of ataxic symptoms in SCA2 and in other SCAs and that positive modulators of SK channels can be used to normalize activity of PCs and alleviate ataxic phenotype in patients with SCA.

Original languageEnglish (US)
Pages (from-to)2840-2851
Number of pages12
JournalJournal of Neurophysiology
Volume115
Issue number6
DOIs
StatePublished - Jun 1 2016

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Purkinje Cells
Transgenic Mice
Chlorzoxazone
Intraperitoneal Injections
Spinocerebellar Ataxias
Small-Conductance Calcium-Activated Potassium Channels
Cell Aging
Neurodegenerative Diseases
Phenotype

Keywords

  • Ataxia
  • Chlorzoxazone
  • Electrophysiology
  • NS8593
  • Purkinje cells
  • SCA2
  • SK channels
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

Cite this

In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model. / Egorova, Polina A.; Zakharova, Olga A.; Vlasova, Olga L.; Bezprozvanny, Ilya B.

In: Journal of Neurophysiology, Vol. 115, No. 6, 01.06.2016, p. 2840-2851.

Research output: Contribution to journalArticle

Egorova, Polina A. ; Zakharova, Olga A. ; Vlasova, Olga L. ; Bezprozvanny, Ilya B. / In vivo analysis of cerebellar Purkinje cell activity in SCA2 transgenic mouse model. In: Journal of Neurophysiology. 2016 ; Vol. 115, No. 6. pp. 2840-2851.
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