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

Abstract

The role of feedforward inhibition onto Purkinje cells during learning is still not well understood. Here, the authors report that selective genetic removal of GABAA receptor–mediated inhibition onto Purkinje cells modulates fine-scale patterns of Purkinje cell activity. These patterns may mediate the induction of downstream plasticity and, ultimately, the consolidation of cerebellar motor learning. 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.