Neuronal activity in the subthalamic nucleus and globus pallidus of patients with Parkinson's disease

grantor: University of TorontoPatients with Parkinson's disease (PD) display bradykinesia, rigidity, and tremor and these symptoms are associated with the loss of dopaminergic input to the striatum of the basal ganglia. The current model of the basal ganglia function predicts that the clinical features of PD are related to elevated firing rates of neurons in the subthalamic nucleus (STN) and globus pallidus internus (GPi). However, it is possible that the discharge pattern of neurons in these nuclei also contributes to parkinsonism. The aim of this project was to characterize the pattern of activity and the population behavior of neurons in the STN and GPi and to elucidate the significance of this activity in PD. This thesis describes work carried out in awake patients with PD during stereotaxic brain surgery. Microelectrode recordings of single neurons or pairs of neurons and macroelectrode recordings of local field potentials were performed in the STN, GPi, and globus pallidus externus (GPe), In addition to a reduction in the firing rates of GPi and STN neurons, the dopaminergic medication apomorphine increased neuronal bursting activity, reduced the incidence of cells with tremor-related oscillations, and reduced the receptive fields of neurons to passive movement in these nuclei. Microinjections of inactivating agents in the STN reversed parkinsonian symptoms, especially limb tremor following inactivation of regions with tremor-related cells. In tremulous patients, many STN cells and some GPi cells were observed to synchronously oscillate at the frequency of limb tremor (3-8 Hz) and/or at higher frequencies (15-30 Hz). Both voluntary movement and dopaminergic medication were found to reduce the 15-30 Hz synchronized oscillations in the STN. Interestingly, none of the neuron pairs examined from the STN or GPi showed cross-correlations indicative of synchronization due to direct synaptic connections or direct common input, suggesting that the synchronization of neuronal activity in the basal ganglia is limited to oscillatory activity. These results indicate that neuronal discharge patterns and the population behavior are related to clinical symptoms of PD and may play an important role in the normal and pathological functioning of the basal ganglia.Ph.D