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

Nat Commun. 2021 Apr 12;12(1):2153. doi: 10.1038/s41467-021-22405-8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Calcium Signaling*
  • Channelrhodopsins / metabolism
  • Dendrites / metabolism*
  • Endocannabinoids / metabolism
  • Mice, Transgenic
  • Motor Activity*
  • Neuronal Plasticity
  • Optogenetics
  • Piperidines / pharmacology
  • Purkinje Cells / metabolism*
  • Pyrazoles / pharmacology
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / metabolism
  • Reflex, Vestibulo-Ocular
  • Wakefulness

Substances

  • Channelrhodopsins
  • Endocannabinoids
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • AM 251