Metabolic effects of nigrostriatal denervation in basal ganglia

In the past, functional changes in the circuitry of the basal ganglia that occur in Parkinson's disease were primarily analyzed with electrophysiologi cal and 2-deoxyglucose measurements. The increased activity of the subthala mic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary t o the loss of dopamineugic-neuron influence on D2-receptor-bearing striato- pallidal neurons. More recently, in situ hybridization studies of cytochrom e oxidase subunit I have confirmed the overactivity of the STN in the parki nsonian state. In addition, this technique has provided evidence that the c hange in STN activity is owing not only to decreased inhibition from the GP e but to hyperactivity of excitatory inputs from the parafascicular nucleus of the thalamus and the pedunculopontine nucleus in the brainstem.