Striatal origin of the pathologic beta oscillations in Parkinson's disease
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McCarthy, M. M., Moore-Kochlacs, C., Xuan Gu, T., Boyden, E. S., Han, X., Kopell, N. J. (2011) Striatal origin of the pathologic beta oscillations in Parkinson’s disease, Proceedings of the National Academy of Sciences 108(28):11620-5.
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 localfield 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.