title: Ventral Medial Thalamic Nucleus Promotes Synchronization of Increased High Beta Oscillatory Activity in the Basal Ganglia-Thalamocortical Network of the Hemiparkinsonian Rat.
abstract: Loss of dopamine is associated with increased synchronization and oscillatory activity in the subthalamic nucleus and basal ganglia (BG) output nuclei in both Parkinson's disease (PD) patients and animal models of PD. We have previously observed substantial increases in spectral power in the 25-40 Hz range in LFPs recorded in the substantia nigra pars reticulata (SNpr) and motor cortex (MCx) in the hemiparkinsonian rat during treadmill walking. The current study explores the hypothesis that SNpr output entrains activity in the ventral medial thalamus (VM) in this frequency range after loss of dopamine, which in turn contributes to entrainment of the MCx and BG. Electrode bundles were implanted in MCx, SNpr, and VM of rats with unilateral dopamine cell lesions. Spiking and LFP activity were recorded during epochs of rest and walking on a circular treadmill. After dopamine cell lesion, 30-36 Hz LFP activity in the VM became more robust during treadmill walking and more coherent with LFP activity in the same range in MCx and SNpr. Infusion of the GABAA antagonist picrotoxin into the VM reduced both high beta power in MCx and SNpr and coherence between MCx and SNpr while temporarily restoring walking ability. Infusion of the GABAA agonist muscimol into the VM also reduced MCx-SNpr coherence and beta power but failed to improve walking. These results support the view that synchronized neuronal activity in the VM contributes to the emergence of high beta oscillations throughout the BG-thalamocortical network in the behaving parkinsonian rat.
  
  
  CONCLUSIONS
  Parkinson's disease symptoms are associated with dramatic increases in synchronized beta range (15-35 Hz) oscillatory local field activity in several brain areas involved in motor control, but the mechanisms promoting this activity and its functional significance remain unresolved. This oscillatory activity can be recorded in awake behaving rats with unilateral dopamine cell lesions using chronically implanted electrodes. Although these rats have motor deficits, they can walk on a circular treadmill in the direction ipsilateral to their lesion. This study establishes a critical role for the ventral medial thalamus in the propagation of this exaggerated beta range oscillatory activity and the sequential entrainment of structures throughout the basal ganglia-thalamocortical loop in the lesioned hemisphere of hemiparkinsonian rats during treadmill walking.
authors.affiliation: Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702.
authors.forename: Elena
authors.initials: E
authors.lastname: Brazhnik
authors.affiliation: Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: McCoy
authors.affiliation: Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Novikov
authors.affiliation: Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Hatch
authors.affiliation: Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-3702 waltersj@ninds.nih.gov.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Walters
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D001611:Beta Rhythm; D002540:Cerebral Cortex / Q000503:physiopathology*; D059290:Dopaminergic Neurons; D005071:Evoked Potentials; D018755:GABA Agonists / Q000494:pharmacology; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology; D011597:Psychomotor Performance; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000187:drug effects; D012146:Rest; D013378:Substantia Nigra / Q000503:physiopathology; D020651:Ventral Thalamic Nuclei / Q000503:physiopathology*; D016138:Walking
chemical_list: D018755:GABA Agonists; D011963:Receptors, GABA-A; D009118:Muscimol
keywords: Parkinson's disease; basal ganglia; beta oscillations; motor cortex; substantia nigra; ventral medial thalamus