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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.

SUBMITTER: Pan MK 

PROVIDER: S-EPMC5127676 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Neuronal firing patterns outweigh circuitry oscillations in parkinsonian motor control.

Pan Ming-Kai MK   Kuo Sheng-Han SH   Tai Chun-Hwei CH   Liou Jyun-You JY   Pei Ju-Chun JC   Chang Chia-Yuan CY   Wang Yi-Mei YM   Liu Wen-Chuan WC   Wang Tien-Rei TR   Lai Wen-Sung WS   Kuo Chung-Chin CC  

The Journal of clinical investigation 20161031 12


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  ...[more]

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