Functional correlates of exaggerated oscillatory activity in basal ganglia output in hemiparkinsonian rats

Exaggerated beta range (13-30 Hz) synchronized activity is observed in the basal ganglia of Parkinson's disease (PD) patients during implantation of deep brain stimulation electrodes and is thought to contribute to the motor symptoms of this disorder. To explore the translational potential of similar activity observed in a rat model of PD, local field potentials (LFPs) and spiking activity in basal ganglia output were characterized in rats with unilateral dopamine cell lesion during a range of behaviors. A circular treadmill was used to assess activity during walking; hemiparkinsonian rats could maintain a steady gait when oriented ipsiversive to the lesioned hemisphere, but were less effective at walking when oriented contraversive to lesion. Dramatic increases in substantia nigra pars reticulata (SNpr) LFP oscillatory activity and spike-LFP synchronization were observed within the beta/low gamma range (12-40 Hz) in the lesioned hemisphere, relative to the non-lesioned hemisphere, with the dominant frequency of spike-LFP entrainment and LFP power varying with behavioral state. At 3 weeks postlesion, the mean dominant entrainment frequency during ipsiversive treadmill walking and grooming was 34 Hz. Other behaviors were associated with lower mean entrainment frequencies: 27-28 Hz during alert non-walking and REM. 17 Hz during rest and 21 Hz during urethane anesthesia with sensory stimulation. SNpr spike-LFP entrainment frequency was stable during individual treadmill walking epochs, but increased gradually over weeks postlesion. In contrast, SNpr LP power in the 25-40 Hz range was greatest at the initiation of each walking epoch, and decreased during walking to stabilize by 6 min at 49% of initial values. Power was further modulated in conjunction with the 1.5 s stepping rhythm. Administration of L-dopa improved contraversive treadmill walking in correlation with a reduction in SNpr 25-40 Hz LFP power and spike synchronization in the dopamine cell lesioned hemisphere. These effects were reversed by the serotonergic 1A agonist, 8-OH-DPAT. While the prominent spike-LP phase locking observed during ongoing motor activity in the hemiparkinsonian rats occurs at frequencies intriguingly higher than in PD patients, the synchronized activity in the SNpr of this animal model has much in common with oscillatory activity recorded from the basal ganglia of the PD patients. Results support the potential of this model for providing insight into relationships between synchronization of basal ganglia output induced by loss of dopamine and motor symptoms in PD. Published by Elsevier Inc.