Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity

J Neurosci. 2014 Feb 5;34(6):2321-30. doi: 10.1523/JNEUROSCI.4547-13.2014.

Abstract

Purkinje cells (PCs) of the cerebellar cortex are necessary for controlling movement with precision, but a mechanistic explanation of how the activity of these inhibitory neurons regulates motor output is still lacking. We used an optogenetic approach in awake mice to show for the first time that transiently suppressing spontaneous activity in a population of PCs is sufficient to cause discrete movements that can be systematically modulated in size, speed, and timing depending on how much and how long PC firing is suppressed. We further demonstrate that this fine control of movement kinematics is mediated by a graded disinhibition of target neurons in the deep cerebellar nuclei. Our results prove a long-standing model of cerebellar function and provide the first demonstration that suppression of inhibitory signals can act as a powerful mechanism for the precise control of behavior.

Keywords: basket cells; disinhibition; eyeblink; forward model; inverse model; molecular layer interneurons.

Publication types

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

MeSH terms

  • Animals
  • Biomechanical Phenomena / physiology
  • Electric Stimulation / methods
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Movement / physiology*
  • Neural Inhibition / physiology*
  • Optogenetics / methods*
  • Photic Stimulation / methods*
  • Purkinje Cells / physiology*