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Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson's disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12–35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD. [ABSTRACT FROM AUTHOR]

The pedunculopontine nucleus (PPN) is composed of a morphologically and neurochemically heterogeneous population of neurons, which is severely affected by Parkinson's disease (PD). However, the role of each subtype of neurons within the PPN in the pathophysiology of PD has not been completely elucidated. In this study, we present the discharge profiles of three classified subtypes of PPN neurons and their alterations after 6-hydroxydopamine (6-OHDA) lesion. Following 6-OHDA lesion, the spike timing of the Type II (GABAergic) and Type III (glutamatergic) neurons had phase-lock with the oscillations in the delta and beta band frequency range in the PPN, respectively. Morphological evidence has shown distinct alteration in three kinds of neurons after 6-OHDA lesion. These findings revealed that the changes in the firing characteristics of neurons in PPN in hemi-parkinsonism rats are closely associated with damaged neuronal morphology, which would make contributions to the divergence of dysfunctions in Parkinsonism. [ABSTRACT FROM AUTHOR]

Beta band (12–30 Hz) hypersynchrony within the basal ganglia-thalamocortical network has been suggested as a hallmark of Parkinson's disease (PD) pathophysiology. Abnormal beta band oscillations are found in the pedunculopontine nucleus (PPN) and primary motor cortex (M1) and are correlated with dopamine depletion. Dopamine acts locomotion and motor performance mainly through dopamine receptors (D1 and D2). However, the precise mechanism by which dopamine receptors regulate beta band electrophysiological activities between the PPN and M1 is still unknown. Here, we recorded the neuronal activity of the PPN and M1 simultaneously by the administration of the drug (SCH23390 and raclopride), selectively blocking the dopamine D1 receptor and D2 receptor. We discovered that the increased coherent activity of the beta band (12–30 Hz) between M1 and PPN in the lesioned group could be reduced and restored by injecting raclopride in the resting and wheel running states. Our studies revealed the unique role of D2 dopamine receptor signaling in regulating β band oscillatory activity in M1 and PPN and their relationship after the loss of dopamine, which contributes to elucidating the underlying mechanism of the pathophysiology of PD. • Increased β frequency band was shown in M1 and PPN in the PD condition. • The increased β frequency band activities could be rescued by the raclopride. • SCH23390 could not correct the increased β band activities. [ABSTRACT FROM AUTHOR]

Abstract Recent studies on the impact of Parkinson's disease (PD) on the thalamostriatal pathway have mainly focused on the structural and functional changes in the thalamus projection to the striatum. Alterations in the electrophysiological activity of the thalamostriatal circuit in PD have not been intensively studied. To further investigate this circuit, parafascicular nucleus (PF) single-unit spikes and dorsal striatum local field potential (LFP) activities were simultaneously recorded in control and 6-hydroxydopamine (6-OHDA)-lesioned rats during inattentive rest or treadmill walking states. We classified the PF neurons into two predominant subtypes (PF I and PF II). During rest state, after dopamine loss, increased PF I spike and striatal LFP coherence was observed in the beta-frequency (12–35 Hz), with changed PF I neuronal firing pattern and unchanged firing rates of the two neuron subtypes. However, in a treadmill walking state, PF II neurons displayed markedly increased coherence to striatal beta oscillations in the dopamine-depleted rats, as well as an altered PF II neuronal firing pattern and significantly decreased firing rates of the two neuron subtypes. The results indicate that in PD animals, state transition from rest to moving, such as treadmill walking, is associated with different PF neuron types and increased spike-LFP synchronization, which may provide new paradigms for understanding and treating PD. Highlights • PF neurons were classified into two predominant subtypes and dopamine loss altered PF neural firing activities. • The alterations of PF neural firing in PD are state-dependent. • Synchronization between single PF neurons with striatum β-frequency oscillations increased after dopamine loss. • The changes of synchronization are associated with different PF neuron subtypes in different states. [ABSTRACT FROM AUTHOR]

• Dopamine receptor agonists were intrastriatally injected into hemiparkinsonism and control rats. • SKF38393 and quinpirole produce a dose-related enhancement in locomotor activity. • SKF38393 and quinpirole induce more ameliorated movement in hemiparkinsonism rats than in control rats. • Quinpirole produced more ameliorated locomotor activity than SKF38393 in hemiparkinsonism rats. Dopamine (DA) in the striatum is essential to influence motor behavior and may lead to movement impairment in Parkinson's disease (PD). The present study examined the different functions of the DA D1 receptor (D1R) and DA D2 receptor (D2R) by intrastriatal injection of the D1R agonist SKF38393 and the D2R agonist quinpirole in 6-hydroxydopamine (6-OHDA)-lesioned and control rats. All rats separately underwent dose-response behavior testing for SKF38393 (0, 0.5, 1.0, and 1.5 μg/site) or quinpirole (0, 1.0, 2.0, and 3.0 μg/site) to determine the effects of the optimal modulating threshold dose. Two behavior assessment indices, the time of latency to fall and the number of steps on a rotating treadmill, were used as reliable readouts of motor stimulation variables for quantifying the motor effects of the drugs. The findings indicate that at threshold doses, SKF38393 (1.0 μg/site) and quinpirole (1.0 μg/site) produce a dose-dependent increase in locomotor activity compared to vehicle injection. The ameliorated behavioral responses to either SKF38393 or quinpirole in lesioned rats were greater than those in unlesioned control rats. Moreover, the dose-dependent increase in locomotor capacity for quinpirole was greater than that for SKF38393 in lesioned rats. These results can clarify several key issues related to DA receptors directly and may provide a basis for exploring the potential of future selective dopamine therapies for PD in humans. [ABSTRACT FROM AUTHOR]