title: 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.
authors: Ming-Kai
authors: MK
authors: Pan
authors: Sheng-Han
authors: SH
authors: Kuo
authors: Chun-Hwei
authors: CH
authors: Tai
authors: Jyun-You
authors: JY
authors: Liou
authors: Ju-Chun
authors: JC
authors: Pei
authors: Chia-Yuan
authors: CY
authors: Chang
authors: Yi-Mei
authors: YM
authors: Wang
authors: Wen-Chuan
authors: WC
authors: Liu
authors: Tien-Rei
authors: TR
authors: Wang
authors: Wen-Sung
authors: WS
authors: Lai
authors: Chung-Chin
authors: CC
authors: Kuo
mesh_terms: D000818:Animals; D001683:Biological Clocks; D046690:Deep Brain Stimulation; D018476:Hypokinesia / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009474:Neurons; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000473:pathology / Q000503:physiopathology*