Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates

The basal ganglia are currently viewed as components of segregated corticos ubcortical reentrant circuits. One of these circuits, the "motor" circuit, is critically involved in the development of parkinsonian motor signs. Curr ent pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activit y in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact an d parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has re ceived far less attention. This study in primates represents a comparison o f the effects of parkinsonism, induced by injections of the dopaminergic ne urotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), on the neuron al discharge in the GPi and SNr. These electrophysiologic recording experim ents were carried out in three African green and two rhesus monkeys. One hu ndred and twenty-four neurons were recorded in the GPi before treatment wit h MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded befor e treatment with MPTP, and 41 cells thereafter. MPTP induced a non-signific ant increase in the average discharge rate and a significant decrease in th e median interspike interval length (ISI) in the GPi (by 13%), whereas no c hanges were detected in either parameter in the SNr. The average ISI distri butions were markedly asymmetric in both structures, and could be modeled b y a logarithmic normal distribution. With the MPTP treatment, the mode of t he ISI distribution fell by 24% in the GPi (P less than or equal to 0.01), whereas it did not change significantly in the SNr. An algorithm that detec ts burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action poten tials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrela tion analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0 .8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonis m, but that the changes in the SNr are less pronounced then those seen in t he GPi.