Article abstract
Nature Neuroscience 12, 1042 - 1049 (2009)
Published online: 5 July 2009 | doi:10.1038/nn.2348
Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning
Peer Wulff1,7, Martijn Schonewille2,7, Massimiliano Renzi3, Laura Viltono4, Marco Sassoè-Pognetto4, Aleksandra Badura2, Zhenyu Gao2, Freek E Hoebeek2, Stijn van Dorp5, William Wisden1,6, Mark Farrant3 & Chris I De Zeeuw2,5
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-
2) in which GABAA 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.
- Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen, UK.
- Department of Neuroscience, Erasmus MC, Rotterdam, The Netherlands.
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
- Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin and National Institute of Neuroscience-Italy, Turin, Italy.
- Netherlands Institute for Neuroscience, Royal Academy of Sciences, Amsterdam, The Netherlands.
- Division of Cell and Molecular Biology, Imperial College, London, UK.
- These authors contributed equally to this work.
Correspondence to: Chris I De Zeeuw2,5 e-mail: c.dezeeuw@erasmusmc.nl
Correspondence to: Mark Farrant3 e-mail: m.farrant@ucl.ac.uk
Correspondence to: William Wisden1,6 e-mail: w.wisden@imperial.ac.uk
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