title: Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat.
abstract: Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) of untreated patients implanted with stimulation electrodes for the treatment of Parkinson's disease (PD) demonstrate strong coherence with the cortical electroencephalogram over the beta-frequency range (15-30 Hz). However, studies in animal models of PD emphasize increased temporal coupling in cortico-basal ganglia circuits at substantially lower frequencies, undermining the potential usefulness of these models. Here we show that 6-hydroxydopamine (6-OHDA) lesions of midbrain dopamine neurons are associated with significant increases in the power and coherence of beta-frequency oscillatory activity present in LFPs recorded from frontal cortex and STN of awake rats, as compared with the healthy animal. Thus, the pattern of synchronization between population activity in the STN and cortex in the 6-OHDA-lesioned rodent model of PD closely parallels that seen in the parkinsonian human. The peak frequency of coherent activity in the beta-frequency range was increased in lesioned animals during periods of spontaneous and sustained movement. Furthermore, administration of the dopamine receptor agonist apomorphine to lesioned animals suppressed beta-frequency oscillations, and increased coherent activity at higher frequencies in the cortex and STN, before producing the rotational behaviour indicative of successful lesion. Taken together, these results support a crucial role for dopamine in the modulation of population activity in cortico-basal ganglia circuits, whereby dopaminergic mechanisms effectively filter out synchronized, rhythmic activity at beta-frequencies at the systems level, and shift temporal couplings in these circuits to higher frequencies. These changes may be important in regulating movement.
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sharott
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Magill
authors.forename: Daniel
authors.initials: D
authors.lastname: Harnack
authors.forename: Andreas
authors.initials: A
authors.lastname: Kupsch
authors.forename: Wassilios
authors.initials: W
authors.lastname: Meissner
authors.forename: Peter
authors.initials: P
authors.lastname: Brown
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001611:Beta Rhythm / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000172:deficiency*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D012399:Rotation; D013057:Spectrum Analysis / Q000379:methods; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D018663:Adrenergic Agents; D018491:Dopamine Agonists; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine