Bicuculline-Induced Chorea Manifests in Focal Rather Than Globalized Abnormalities in the Activation of the External and Internal Globus Pallidus

Abstract

Chorea is a basal-ganglia (BG) related hyperkinetic movement disorder characterized by irregular continuous involuntary movements. Chorea and related hyperbehavioral disorders may be induced in behaving primates by local microinjections of the GABAA antagonist bicuculline to the globus pallidus externus (GPe). We performed multielectrode extracellular recordings in the GPe and in the globus pallidus internus (GPi) before, during, and after bicuculline microinjections. Bicuculline led to an increase in the firing rate and a change in the firing pattern of GPe neurons. Two types of abnormal neuronal firing patterns were detected in GPe neurons close to the bicuculline microinjection site: continuous high-frequency activity and bistable activity, in which neurons transitioned between high-frequency and complete cessation of firing. Neuronal activity remained uncorrelated within and between the GPe and the GPi, with no evidence for propagation of the focal GPe abnormal activity downstream to the GPi. Despite reduction in the information capacity of bicuculline-affected GPe neurons, the ability to encode behavioral events was maintained. We found similar responses of GPe neurons to bicuculline in vitro in the rat, suggesting a basic cellular mechanism underlying these abnormal firing patterns. These results demonstrate that chorea is associated with focal neuronal changes that are not complemented by global changes in the BG nuclei. This suggests a mechanism of stochastic phasic alteration of BG control leading to the chaotic nature of chorea. Thus rather than imposing a globalized state of cortical excitability, chorea might be associated with changes in internal information processing within the BG.