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-Δγ2) 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.
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We thank L. Cheyne, D. Massie, M. Rutteman, R. Avila Freire, E. Dalm and J.v.d. Burg for their excellent technical assistance, and D. Andersson and L. Kelly for their participation in the initial electrophysiological studies. This work was supported by the J. Ernest Tait Estate Aberdeen (W.W.), a Medical Research Council program grant G0800399 (P.W. and W.W.), the Royal Society (P.W.), the Institute Pasteur-Fondazione Cenci Bolognetti (M.R.), a Wellcome Trust program grant (M.F.), Regione Piemonte (Ricerca Scientifica Applicata A218 and Ricerca Sanitaria Finalizzata 2006) and Compagnia di San Paolo (M.S.-P.), the Dutch Organization for Medical Sciences (C.I.D.Z.), Life Sciences (C.I.D.Z.), Senter (Neuro-Bsik, C.I.D.Z.), Prinses Beatrix Fonds (C.I.D.Z.), and the SENSOPAC (SENSOrimotor structuring of Perception and Action for Emerging Cognition) program of the European Community (C.I.D.Z.).
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Wulff, P., Schonewille, M., Renzi, M. et al. Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci 12, 1042–1049 (2009). https://doi.org/10.1038/nn.2348
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