Motor complications associated with Parkinson's disease (PD) range from akinesia to dyskinesia, depending on disease duration and L-DOPA treatment. This dissertation utilized a rodent model of PD to investigate how neuronal activity in the substantia nigra pars reticulata (SNpr), a basal ganglia output nucleus, is differentially expressed in intact and dopamine (DA) depleted states during rest and walking and after acute and chronic L-DOPA treatment. Single unit and local field potential (LFP) recordings were conducted bilaterally in the SNpr in rats with unilateral DA cell lesions induced by 6-hydroxydopamine. Electromyography (EMG) activity was recorded bilaterally from scapularis muscle. Results demonstrated significantly greater low beta frequency (12–25 Hz) power at rest and high beta/low gamma frequency (25–40 Hz) power during walking in the SNpr of the lesioned hemisphere compared with control and non-lesioned hemispheres. Increases in spike-triggered LFP waveform average amplitudes showed that neuronal spiking was more synchronized with beta range oscillations at rest and high beta/low gamma during walking in the lesioned hemisphere SNpr. Rats were then treated once daily with 25 mg/kg L-DOPA + 6.25 mg/kg benserazide for 14 days. L-DOPA induced rotation and firing rate changes which were linearly correlated with time. In the lesioned hemisphere, SNpr firing rate decreases were significantly correlated with rotation rate increases after both 1 and 14 days of L-DOPA treatment. On Day 14, limb dyskinesias were evident after rotations wore off. EMG activity in the 5–9 Hz range was greater in the impaired limb than the healthy limb during dyskinetic episodes. SNpr spike trains in the lesioned hemisphere showed modest but significantly greater coherence with the EMG 5–9 Hz oscillations in the dyskinetic limb. These data confirm predictions that firing rate changes in SNpr correlate strongly with rotational behavior and show that SNpr firing pattern correlates weakly with dyskinetic movements. Overall, results provide insight into the specific changes in basal ganglia output that underlie motor dysfunction in PD. Examining firing rates and beta/gamma frequency activity in nuclei that receive SNpr output will further elucidate how these changes in SNpr activity affect downstream nuclei and contribute to PD symptoms.
|School:||Arizona State University|
|School Location:||United States -- Arizona|
|Source:||DAI-B 70/04, Dissertation Abstracts International|
|Subjects:||Neurosciences, Behavioral psychology, Physiological psychology|
|Keywords:||Basal ganglia, Bradykinesia, Dopamine, Levodopa-induced movements, Local field potentials, Oscillations, Parkinson's disease, Substantia nigra pars reticulata|
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