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J Clin Invest. 2016 Dec 1;126(12):4516-4526. doi: 10.1172/JCI88170. Epub 2016 Oct 31.

Neuronal firing patterns outweigh circuitry oscillations in parkinsonian motor control.

Abstract

Neuronal oscillations at beta frequencies (20-50 Hz) in the cortico-basal ganglia circuits have long been the leading theory for bradykinesia, the slow movements that are cardinal symptoms in Parkinson's disease (PD). The beta oscillation theory helped to drive a frequency-based design in the development of deep brain stimulation therapy for PD. However, in contrast to this theory, here we have found that bradykinesia can be completely dissociated from beta oscillations in rodent models. Instead, we observed that bradykinesia is causatively regulated by the burst-firing pattern of the subthalamic nucleus (STN) in a feed-forward, or efferent-only, mechanism. Furthermore, STN burst-firing and beta oscillations are two independent mechanisms that are regulated by different NMDA receptors in STN. Our results shift the understanding of bradykinesia pathophysiology from an interactive oscillatory theory toward a feed-forward mechanism that is coded by firing patterns. This distinct mechanism may improve understanding of the fundamental concepts of motor control and enable more selective targeting of bradykinesia-specific mechanisms to improve PD therapy.

PMID:
27797341
PMCID:
PMC5127676
[Available on 2017-03-01]
DOI:
10.1172/JCI88170
[Indexed for MEDLINE]
Free PMC Article

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