title: Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum.
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.
authors.affiliation: Motor Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Saeka
authors.initials: S
authors.lastname: Tomatsu
authors.affiliation: Frontal Lobe Function Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tsunoda
authors.affiliation: Motor Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
authors.forename: Jongho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America; Center for the Neural Basis of Cognition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Donna S
authors.initials: DS
authors.lastname: Hoffman
authors.affiliation: Motor Disorders Project, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kakei
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002525:Cerebellar Cortex / Q000502:physiology; D002529:Cerebellar Nuclei / Q000502:physiology; D002531:Cerebellum / Q000502:physiology*; D008251:Macaca; D009068:Movement / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology*