Reversible Block of Cerebellar Outflow Reveals Cortical Circuitry for Motor Coordination

Cell Rep. 2019 May 28;27(9):2608-2619.e4. doi: 10.1016/j.celrep.2019.04.100.

Abstract

Coordinated movements are achieved by well-timed activation of selected muscles. This process relies on intact cerebellar circuitry, as demonstrated by motor impairments following cerebellar lesions. Based on anatomical connectivity and symptoms observed in cerebellar patients, we hypothesized that cerebellar dysfunction should disrupt the temporal patterns of motor cortical activity, but not the selected motor plan. To test this hypothesis, we reversibly blocked cerebellar outflow in primates while monitoring motor behavior and neural activity. This manipulation replicated the impaired motor timing and coordination characteristic of cerebellar ataxia. We found extensive changes in motor cortical activity, including loss of response transients at movement onset and decoupling of task-related activity. Nonetheless, the spatial tuning of cells was unaffected, and their early preparatory activity was mostly intact. These results indicate that the timing of actions, but not the selection of muscles, is regulated through cerebellar control of motor cortical activity.

Keywords: cerebellar ataxia; cerebellar-thalamo-cortical; high-frequency stimulation; inter-joint coordination; motor timing; noise correlation; non-human primates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping
  • Cerebellar Diseases / physiopathology*
  • Cerebellum / physiology*
  • Female
  • Macaca fascicularis
  • Motor Cortex / physiology*
  • Movement / physiology*
  • Neurons / physiology*