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 Ca²⁺ transients with high-intensity stimuli initiating dendritic spiking that additionally contributes to the Ca²⁺ response. Channelrhodopsin-2-evoked Ca²⁺ transients potentiate co-active parallel fiber synapses; depression occurs when Ca²⁺ 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 Ca²⁺ responses. In contrast, pairing with large-magnitude Ca²⁺ 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 Ca²⁺ elevation. Our results establish a causal relationship among Purkinje cell Ca²⁺ signal size, opposite-polarity plasticity induction, and bidirectional motor learning.