RRC ID 20946
Author McCairn KW, Iriki A, Isoda M.
Title Global dysrhythmia of cerebro-basal ganglia-cerebellar networks underlies motor tics following striatal disinhibition.
Journal J. Neurosci.
Abstract Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.
Volume 33(2)
Pages 697-708
Published 2013-1-9
DOI 10.1523/JNEUROSCI.4018-12.2013
PII 33/2/697
PMID 23303948
MeSH Animals Basal Ganglia / drug effects Basal Ganglia / physiopathology* Behavior, Animal / physiology Bicuculline / pharmacology Cerebellum / drug effects Cerebellum / physiopathology* Data Interpretation, Statistical Electrodes, Implanted GABA Antagonists / pharmacology Macaca Male Motor Cortex / drug effects Motor Cortex / physiopathology* Neostriatum / physiopathology* Nerve Net / drug effects Nerve Net / physiopathology* Putamen / physiology Tics / chemically induced Tics / physiopathology*
IF 5.971
Times Cited 23
WOS Category NEUROSCIENCES
Resource
Japanese macaques