title: Subthalamic discharges as a causal determinant of parkinsonian motor deficits.
abstract: OBJECTIVE
  We have reported that intrinsic membrane properties, especially T-type Ca2+ channels, play a key role in the genesis of burst discharges in the subthalamic nucleus (STN) and parkinsonian locomotor symptoms. Whether deep brain stimulation (DBS) exerts its clinical benefits on Parkinson disease (PD) with changes in T currents or other conductances, however, remains elusive.
  
  
  METHODS
  Different stimulation protocols, including constant currents of opposite polarity, were applied to STN in vivo or in vitro, and the electrophysiological and behavioral effects were documented in normal and parkinsonian rodents. The effect of correlatively adjusted DBS protocols was also explored in 3 PD patients.
  
  
  RESULTS
  Delivery of negative constant current into STN dramatically ameliorated locomotor deficits in parkinsonian rats. It also depolarized STN neurons and decreased T-channel availability as well as burst discharges. In contrast, delivery of positive constant currents to STN induced PD-like locomotor deficits and increased STN burst discharges in normal rats. In addition, the therapeutic effect of DBS was greatly improved in 3 PD patients simply by increasing the pulse width from 60 to 240 microseconds, even at a lower stimulation frequency of 60 Hz.
  
  
  CONCLUSIONS
  The increased tendency of STN burst discharges may by itself serve as a direct cause of parkinsonian locomotor deficits, even in the absence of deranged dopaminergic innervation. Effective DBS therapy in PD very likely relies on adequate depolarization, and consequent modification of the relevant ionic currents and discharge patterns, of STN neurons.
authors.affiliation: Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chun-Hwei
authors.initials: CH
authors.lastname: Tai
authors.forename: Ming-Kai
authors.initials: MK
authors.lastname: Pan
authors.forename: Janice Janing
authors.initials: JJ
authors.lastname: Lin
authors.forename: Chen-Syuan
authors.initials: CS
authors.lastname: Huang
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Yang
authors.forename: Chung-Chin
authors.initials: CC
authors.lastname: Kuo
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D046690:Deep Brain Stimulation / Q000379:methods; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000150:complications* / Q000473:pathology / Q000628:therapy*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D020531:Subthalamic Nucleus / Q000473:pathology* / Q000502:physiology*; D013565:Sympatholytics / Q000633:toxicity; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase