Functional Interactions Between the Parafascicular Thalamic Nucleus and Motor Cortex Are Altered in Hemiparkinsonian Rat.

Parkinson's disease (PD) is characterized by aberrant discharge patterns and exaggerated oscillatory activity within basal ganglia-thalamocortical circuits. We have previously observed substantial alterations in spike and local field potential (LFP) activities recorded in the thalamic parafascicular nucleus (PF) and motor cortex (M1), respectively, of hemiparkinsonian rats during rest or catching movements. This study explored whether the mutual effects of the PF and M1 depended on the amplitude and phase relationship in their identified neuron spikes or group rhythmic activities. Microwire electrode arrays were paired and implanted in the PF and M1 of rats with unilateral dopaminergic cell lesions. The results showed that the identified PF neurons exhibited aberrant cell type-selective firing rates and preferential and excessive phase-locked firing to cortical LFP oscillations mainly at 12-35 Hz (beta frequencies), consistent with the observation of identified M1 neurons with ongoing PF LFP oscillations. Experimental evidence also showed a decrease in phase-locking at 0.7-12 Hz and 35-70 Hz in the PF and M1 circuits in the hemiparkinsonian rats. Furthermore, anatomical evidence was provided for the existence of afferent and efferent bidirectional reciprocal connectivity pathways between the PF and M1 using an anterograde and retrograde neuroanatomical tracing virus. Collectively, our results suggested that multiple alterations may be present in regional anatomical and functional modes with which the PF and M1 interact, and that parkinsonism-associated changes in PF integrate M1 activity in a manner that varies with frequency, behavioral state, and integrity of the dopaminergic system.

Beta band modulation by dopamine D2 receptors in the primary motor cortex and pedunculopontine nucleus in a rat model of Parkinson's disease.

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 ß 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.

Effects of intrastriatal injection of the dopamine receptor agonist SKF38393 and quinpirole on locomotor behavior 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.

Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats.

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.

Electrophysiological and Neurochemical Considerations of Distinct Neuronal Populations in the Rat Pedunculopontine Nucleus and Their Responsiveness Following 6-Hydroxydopamine Lesions.

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.

State-Dependent Spike and Local Field Synchronization between the Thalamic Parafascicular Nucleus and the Dorsal Striatum in a Rat Model of Parkinson's Disease.

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.

[Influence of needle-pricking bleeding combined with pulling-rotating manipulation on blood rheology in patients with vertebral artery type cervical spondylosis].

OBJECTIVE: To observe the effect of needle-pricking bleeding combined with pulling-rotating manipulation and simple manipulation on blood rheology in vertebral artery type cervical spondylosis (VATCS) patients, so as to analyze their mechanisms in relieving VATCS. METHODS: A total of 198 VATCS patients were randomly divided into treatment group (n=101) which was treated with needle-pricking plus pulling-rotating manipulation, and control group (n=97) which was treated with simple pulling-rotating manipulation, according to the random number table. The treatment was given once every 7 days, 9 times altogether. The peak systolic blood flow velocity (Vpeak), end-diastolic blood velocity (Vmin), pulsatility index (PI) and resistent index (RI) of bilateral vertebral arteries (VA) and basilar artery (BA) were detected by transcranial doppler sonography (TCD). Whole blood apparent viscosity and the plasma viscosity in the treatment group were determined by using a blood viscosimeter. RESULTS: Of the 101 and 97 VATCS cases in the treatment and control groups, 62 (61.38%) and 12 (12.37%) were cured basically, 23 (22.77%) and 26 (26.80%) experienced marked improvement, 14 (13.86%) and 41 (42.27%) were improved. 2 (1.98%) and 18 (18.55%) failed in the treatment, with the total effective rates being 98.01% and 81.44% separately. The effective rate of the treatment group was significantly higher than that of control group (P<0.05). Compared with pretreatment, Vpeak and Vmin of the bilateral VA and BA in the treatment group, and Vpeak of the right VA in the control group increased significantly (P<0.01, P<0.05), PI and RI of the bilateral VA and BA in the treatment group, and PI and RI of the right VA in the control group decreased significantly (P<0.01, P<0.05), suggesting a marked reduction of the vascular resistance and an apparent increase of the cerebral blood supply after the treatment. The therapeutic effects of the above-mentioned indexes of treatment group were significantly superior to those of the control group (P<0.05). In comparison with pre-treatment, the whole blood apparent viscosity (high, medium and low shear rates) and plasma viscosity of the treatment group post-treatment were obviously reduced (P<0.01, P<0.05). CONCLUSION: Needle-pricking therapy combined with pulling-rotating manipulation can significantly improve VATCS patients' clinical symptoms, which may be closely related to its effects in lowering vascular blood resistance and blood viscosity and increasing cerebral blood supply.

[Controlled study on needle-pricking therapy combined with spinal massage for treatment of ankylosing spondylitis].

OBJECTIVE: To observe the therapeutic effect of needle-pricking therapy combined with spinal massage on ankylosing spondylitis and to probe into the mechanism. METHODS: Ninety-three cases who were definitely diagnosed as having ankylosing spondylitis at active stage were randomly divided into a medication group (n=46) and an observation group (n=47). The observation group were treated by needle-pricking the main points, Neck No. 2 nerve, Neck No. 5 nerve point, etc., combined with spinal rotation massage, and the medication group were treated with Azulfidine. Changes of cumulative score of arthralgia and arthroncus, function of joint, Keitel test, and ESR and CRP before and after treatment were observed. RESULTS: The effective rate and the markedly effective rate were 95.8%0 and 68.1% in the observation group and 78.3% and 23.9% in the medication group, respectively, the former being significantly better than the latter (P < 0.01). CONCLUSION: Needle-pricking therapy combined with spinal massage has a significant therapeutic effect with a steady and long-term effect for treatment of ankylosing spondylitis at active stage.