In Vivo Analysis of the Climbing Fiber-Purkinje Cell Circuit in SCA2-58Q Transgenic Mouse Model

Polina A. Egorova, Alexandra V. Gavrilova, Ilya B. Bezprozvanny

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Cerebellar Purkinje cells (PCs) and cerebellar pathways are primarily affected in many autosomal dominant cerebellar ataxias. PCs generate complex spikes (CS) in vivo when activated by climbing fiber (CF) which rise from the inferior olive. In this study, we investigated the functional state of the CF-PC circuitry in the transgenic mouse model of spinocerebellar ataxia type 2 (SCA2), a polyglutamine neurodegenerative genetic disease. In our experiments, we used an extracellular single-unit recording method to compare the PC activity pattern and the CS shape in age-matched wild-type mice and SCA2-58Q transgenic mice. We discovered no alterations in the CS properties of PCs in aging SCA2 mice. To examine the integrity of the olivocerebellar pathway, we applied harmaline, an alkaloid that acts directly on the inferior olive neurons. The pharmacological stimulation of olivocerebellar circuit by harmaline uncovered disturbances in SCA2-58Q PC activity pattern and in the complex spike shape when compared with age-matched wild-type cells. The abnormalities in the CF-PC circuitry were aggravated with age. We propose that alterations in CF-PC circuitry represent one of potential causes of ataxic symptoms in SCA2 and in other SCAs.

Original languageEnglish (US)
Pages (from-to)590-600
Number of pages11
JournalCerebellum
Volume17
Issue number5
DOIs
StatePublished - Oct 1 2018

Keywords

  • Cerebellar cortex
  • Harmaline
  • Purkinje cells
  • Spinocerebellar ataxias
  • Transgenic mice

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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