SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning–specific memory traces

Giorgio Grasselli, Henk Jan Boele, Heather K. Titley, Nora Bradford, Lisa van Beers, Lindsey Jay, Gerco C. Beekhof, Silas E. Busch, Chris I. de Zeeuw, Martijn Schonewille, Christian Hansel

Research output: Contribution to journalArticle

Abstract

Neurons store information by changing synaptic input weights. In addition, they can adjust their membrane excitability to alter spike output. Here, we demonstrate a role of such “intrinsic plasticity” in behavioral learning in a mouse model that allows us to detect specific consequences of absent excitability modulation. Mice with a Purkinje-cell–specific knockout (KO) of the calcium-activated K+ channel SK2 (L7-SK2) show intact vestibulo-ocular reflex (VOR) gain adaptation but impaired eyeblink conditioning (EBC), which relies on the ability to establish associations between stimuli, with the eyelid closure itself depending on a transient suppression of spike firing. In these mice, the intrinsic plasticity of Purkinje cells is prevented without affecting long-term depression or potentiation at their parallel fiber (PF) input. In contrast to the typical spike pattern of EBC-supporting zebrin-negative Purkinje cells, L7-SK2 neurons show reduced background spiking but enhanced excitability. Thus, SK2 plasticity and excitability modulation are essential for specific forms of motor learning.

Original languageEnglish
Article numbere3000596
JournalPLoS Biology
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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    Grasselli, G., Boele, H. J., Titley, H. K., Bradford, N., van Beers, L., Jay, L., Beekhof, G. C., Busch, S. E., de Zeeuw, C. I., Schonewille, M., & Hansel, C. (2020). SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning–specific memory traces. PLoS Biology, 18(1), [e3000596]. https://doi.org/10.1371/journal.pbio.3000596