Bicuculline induced chorea manifests in focal rather than globalized 2 abnormalities in the activation of the external and internal globus 3 pallidus 4 5 6

27 Chorea is a basal-ganglia (BG) related hyperkinetic movement disorder characterized by 28 irregular continuous involuntary movements. Chorea and related hyper-behavioral disorders 29 may be induced in behaving primates by local microinjections of the GABA-A antagonist 30 bicuculline in the globus pallidus externus (GPe). We performed multi-electrode extracellular 31 recordings in the GPe and in the globus pallidus internus (GPi) before, during and after 32 bicuculline microinjections. Bicuculline led to an increase in the firing rate and a change in the 33 firing pattern of GPe neurons. Two types of abnormal neuronal firing patterns were detected in 34 GPe neurons close to the bicuculline microinjection site: continuous high-frequency activity, 35 and bistable activity in which neurons transitioned between high-frequency and complete 36 cessation of firing. Neuronal activity remained uncorrelated within and between the GPe and 37 the GPi with no evidence of propagation of the focal GPe abnormal activity downstream to the 38 GPi. Despite reduction in the information capacity of bicuculline affected GPe neurons, the 39 ability to encode behavioral events was maintained. We found similar responses of GPe 40 neurons to bicuculline in-vitro in the rat, suggesting a basic cellular mechanism underlying 41 these abnormal firing patterns. These results demonstrate that chorea is associated with focal 42 neuronal changes that are not complemented by global changes in the BG internal and output 43 nuclei. This suggests a mechanism of stochastic phasic alteration of BG control leading to the 44 chaotic nature of chorea. Thus, rather than imposing a globalized state of cortical excitability, 45 chorea might be associated with changes in internal information processing within the BG. 46