title: Striatal origin of the pathologic beta oscillations in Parkinson's disease.
abstract: Enhanced oscillations at beta frequencies (8-30 Hz) are a signature neural dynamic pathology in the basal ganglia and cortex of Parkinson's disease patients. The mechanisms underlying these pathological beta oscillations remain elusive. Here, using mathematical models, we find that robust beta oscillations can emerge from inhibitory interactions between striatal medium spiny neurons. The interaction of the synaptic GABAa currents and the intrinsic membrane M-current promotes population oscillations in the beta frequency range. Increased levels of cholinergic drive, a condition relevant to the parkinsonian striatum, lead to enhanced beta oscillations in the striatal model. We show experimentally that direct infusion of the cholinergic agonist carbachol into the striatum, but not into the neighboring cortex, of the awake, normal rodent induces prominent beta frequency oscillations in the local field potential. These results provide evidence for amplification of normal striatal network dynamics as a mechanism responsible for the enhanced beta frequency oscillations in Parkinson's disease.
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, MA 02215, USA. mmccart@bu.edu
authors.forename: M M
authors.initials: MM
authors.lastname: McCarthy
authors.forename: C
authors.initials: C
authors.lastname: Moore-Kochlacs
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: E S
authors.initials: ES
authors.lastname: Boyden
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.forename: N
authors.initials: N
authors.lastname: Kopell
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001611:Beta Rhythm / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000008:administration & dosage; D018679:Cholinergic Agonists / Q000008:administration & dosage; D004298:Dopamine / Q000502:physiology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D009415:Nerve Net / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000503:physiopathology*; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D005680:gamma-Aminobutyric Acid; D002217:Carbachol; D004298:Dopamine