This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1107748108/-/DCSupplemental.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.National Science Foundation (U.S.). (Grant DMS-0717670)National Science Foundation (U.S.). (Director’s New Innovator Award DP2 OD002002-01)Helen Hay Whitney Foundation FellowshipUnited States. National Institutes of Health (Grant K99MH085944)National Institute of Neurological Disorders and Stroke (U.S.) (Grant 1 R01 NS062955-01)