期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 28, 页码 11620-11625出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1107748108
关键词
computational model; acetylcholine; muscarinic; mouse
资金
- National Science Foundation [DMS-0717670]
- National Institutes of Health [DP2 OD002002-01, K99MH085944]
- Helen Hay Whitney Foundation
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [1 R01 NS062955-01]
- Division Of Mathematical Sciences
- Direct For Mathematical & Physical Scien [1042134] Funding Source: National Science Foundation
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.
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