Autonomous Purkinje cell activation instructs bidirectional motor learning through evoked dendritic calcium signaling

The signals in cerebellar Purkinje cells sufficient to instruct motor learning have not been systematically determined. Therefore, we applied optogenetics in mice to autonomously excite Purkinje cells and measured the effect of this activity on plasticity induction and adaptive behavior. Ex vivo, excitation of channelrhodopsin-2-expressing Purkinje cells elicits dendritic Ca(2+) transients with high-intensity stimuli initiating dendritic spiking that additionally contributes to the Ca(2+) response. Channelrhodopsin-2-evoked Ca(2+) transients potentiate co-active parallel fiber synapses; depression occurs when Ca(2+) responses were enhanced by dendritic spiking. In vivo, optogenetic Purkinje cell activation drives an adaptive decrease in vestibulo-ocular reflex gain when vestibular stimuli are paired with relatively small-magnitude Purkinje cell Ca(2+) responses. In contrast, pairing with large-magnitude Ca(2+) responses increases vestibulo-ocular reflex gain. Optogenetically induced plasticity and motor adaptation are dependent on endocannabinoid signaling, indicating engagement of this pathway downstream of Purkinje cell Ca(2+) elevation. Our results establish a causal relationship among Purkinje cell Ca(2+) signal size, opposite-polarity plasticity induction, and bidirectional motor learning.