The role of the subthalamic nucleus in experimental chorea. Evidence from 2-deoxyglucose metabolic mapping and horseradish peroxidase tracing studies

Abstract

In previous studies we have shown that hemichorea can be induced in the conscious monkey by localized injection of gamma-aminobutyric acid (GABA) antagonists into the contralateral lentiform complex. It has been argued that the primary site of drug action in inducing chorea is the lateral segment of the globus pallidus. In the present study, the neural mechanisms which underlie this experimental dyskinesia were investigated by two separate approaches. First, the efferent projections of the lentiform complex were mapped using neuroanatomical tracing techniques. This involved injecting horseradish peroxide into sites which had previously given chorea when injected with the GABA antagonist bicuculline. Secondly, the 2-deoxyglucose (2-DG) metabolic mapping technique was applied to animals during active dyskinesia. This procedure permitted the autoradiographic measurement of local cerebral glucose uptake which was used as an index of regional synaptic activity. In both instances, the strongest labelling was seen in the dorsolateral region of the subthalamic nucleus. On the basis of this finding it is suggested that the pallidosubthalamic pathway plays a crucial role in the mediation of experimentally-induced chorea. Specifically, the pallidosubthalamic pathway arising from the lateral pallidal segment is abnormally overactive, which causes physiological inhibition of the subthalamic nucleus. The pattern of 2-DG uptake in the medial segment of the globus pallidus and thalamus was similar to that seen in animals with experimentally-induced ballism. This similarity is interpreted as suggesting that a common neural mechanism underlies both experimentally-induced chorea and ballism.