Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning

Peer Wulff, Martijn Schonewille, Massimiliano Renzi, Laura Viltono, Marco Sassoè-Pognetto, Aleksandra Badura, Zhenyu Gao, Freek E Hoebeek, Stijn van Dorp, William Wisden, Mark Farrant, Chris I De Zeeuw

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Although feedforward inhibition onto Purkinje cells was first documented 40 years ago, we understand little of how inhibitory interneurons contribute to cerebellar function in behaving animals. Using a mouse line (PC-Deltagamma2) in which GABA(A) receptor-mediated synaptic inhibition is selectively removed from Purkinje cells, we examined how feedforward inhibition from molecular layer interneurons regulates adaptation of the vestibulo-ocular reflex. Although impairment of baseline motor performance was relatively mild, the ability to adapt the phase of the vestibulo-ocular reflex and to consolidate gain adaptations was strongly compromised. Purkinje cells showed abnormal patterns of simple spikes, both during and in the absence of evoked compensatory eye movements. On the basis of modeling our experimental data, we propose that feedforward inhibition, by controlling the fine-scale patterns of Purkinje cell activity, enables the induction of plasticity in neurons of the cerebellar and vestibular nuclei.
Original languageEnglish
Pages (from-to)1042-1049
Number of pages8
JournalNature Neuroscience
Volume12
Issue number8
DOIs
Publication statusPublished - 2009

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Keywords

  • Action Potentials
  • Adaptation, Physiological
  • Animals
  • Cerebellar Cortex
  • Interneurons
  • Learning
  • Mice
  • Mice, Knockout
  • Neural Inhibition
  • Neuronal Plasticity
  • Organ Culture Techniques
  • Purkinje Cells
  • Receptors, GABA-A
  • Reflex, Vestibulo-Ocular
  • Vestibular Nuclei
  • gamma-Aminobutyric Acid

Cite this

Wulff, P., Schonewille, M., Renzi, M., Viltono, L., Sassoè-Pognetto, M., Badura, A., Gao, Z., Hoebeek, F. E., van Dorp, S., Wisden, W., Farrant, M., & De Zeeuw, C. I. (2009). Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nature Neuroscience, 12(8), 1042-1049. https://doi.org/10.1038/nn.2348