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bioRxiv · 10.1101/180455

Propagation of Beta/Gamma Rhythms in the Cortico-Basal Ganglia Circuits of the Parkinsonian Rat

West, T. O.·Berthouze, L.·Farmer, S. F.·Halliday, D.·Litvak, V.·Magill, P. J.·Sharott, A.
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Abstract

Some motor impairments associated with Parkinsons disease are thought to arise from pathological activity in the neuronal networks formed by the basal ganglia (BG) and motor cortex. To evaluate several hypotheses proposed to explain the emergence of pathological oscillations in Parkinsonism, we investigated changes to the directed connectivity in these networks following dopamine depletion. We recorded local field potentials in the cortex and basal ganglia of anesthetized rats rendered Parkinsonian by injection of 6-hydroxydopamine (6-OHDA), with dopamine-intact rats as controls. We performed systematic analyses of the networks using a novel tool for estimation of directed neural interactions, as well as a conditioned variant which permits the analysis of the dependence of a connection upon a third reference signal. We find evidence of the dopamine dependency of both low beta (14-20 Hz) and high beta/low gamma (20-40 Hz) directed interactions within the BG and cortico-BG networks. Notably, 6-OHDA lesions were associated with enhancement of the cortical \"hyperdirect\" connection to the subthalamic nucleus (STN), as well the STNs feedback to the cortex and striatum. We find beta synchronization to be robust to conditioning using signals from any one structure. Conversely, we find that high beta/gamma drive from the cortex to subcortical regions is weakened by 6-OHDA lesions and is susceptible to conditioning. Furthermore, we provide evidence that gamma is routed from striatum in a pathway that is independent of STN. These results further inform our understanding of the substrates for pathological rhythms in salient brain networks in Parkinsonism.\n\nNew & NoteworthyWe present a novel analysis of electrophysiological recordings in the cortico-basal ganglia network with the aims of evaluating several hypotheses concerning the origins of abnormal brain rhythms associated with Parkinsons disease. We present evidence for changes in the directed connections within the network following chronic dopamine depletion in rodents. These findings speak to the plausibility of a \"short-circuiting\" of the network that gives rise to the conditions from which pathological synchronization may arise.

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West, T. O., Berthouze, L., Farmer, S. F., Halliday, D., Litvak, V., Magill, P. J., Sharott, A.. 2017-08-24. Propagation of Beta/Gamma Rhythms in the Cortico-Basal Ganglia Circuits of the Parkinsonian Rat. https://doi.org/10.1101/180455

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