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Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum

PLoS One. 2014 Oct 3;9(10):e108774. doi: 10.1371/journal.pone.0108774. eCollection 2014.

Abstract

The cerebellum generates its vast amount of output to the cerebral cortex through the dentate nucleus (DN) that is essential for precise limb movements in primates. Nuclear cells in DN generate burst activity prior to limb movement, and inactivation of DN results in cerebellar ataxia. The question is how DN cells become active under intensive inhibitory drive from Purkinje cells (PCs). There are two excitatory inputs to DN, mossy fiber and climbing fiber collaterals, but neither of them appears to have sufficient strength for generation of burst activity in DN. Therefore, we can assume two possible mechanisms: post-inhibitory rebound excitation and disinhibition. If rebound excitation works, phasic excitation of PCs and a concomitant inhibition of DN cells should precede the excitation of DN cells. On the other hand, if disinhibition plays a primary role, phasic suppression of PCs and activation of DN cells should be observed at the same timing. To examine these two hypotheses, we compared the activity patterns of PCs in the cerebrocerebellum and DN cells during step-tracking wrist movements in three Japanese monkeys. As a result, we found that the majority of wrist-movement-related PCs were suppressed prior to movement onset and the majority of wrist-movement-related DN cells showed concurrent burst activity without prior suppression. In a minority of PCs and DN cells, movement-related increases and decreases in activity, respectively, developed later. These activity patterns suggest that the initial burst activity in DN cells is generated by reduced inhibition from PCs, i.e., by disinhibition. Our results indicate that suppression of PCs, which has been considered secondary to facilitation, plays the primary role in generating outputs from DN. Our findings provide a new perspective on the mechanisms used by PCs to influence limb motor control and on the plastic changes that underlie motor learning in the cerebrocerebellum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Cerebellar Cortex / physiology
  • Cerebellar Nuclei / physiology
  • Cerebellum / physiology*
  • Macaca
  • Movement / physiology*
  • Neural Inhibition / physiology*
  • Purkinje Cells / physiology*

Grants and funding

This work was supported by the Tokyo Metropolitan Institute of Medical Science and grants-in-aid from the Japan Science and Technology Agency (PRESTO) to SK (http://www.jst.go.jp/) and from the Ministry of Education, Culture, Sports, Science and Technology in Japan (http://www.mext.go.jp/) (No. 14580784, No. 15016008, No. 16015212, No. 20033029, No. 21500319) to SK and (No. 24650224) to TI and (No. 18700492, No. 20700478) to ST. This project was also supported by NBRP “Japanese Monkeys” through the National BioResource Project of the MEXT Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.