Unilateral lesion of the nigrostriatal pathway induces a transient decrease of firing rate with no change in the firing pattern of neurons of the parafascicular nucleus in the rat.

Electrophysiological recordings of thalamic parafascicular nucleus neurons were done in normal rats and in three groups of rats at different time intervals after injection of 6-hydroxydopamine into the pars compacta of substantia nigra. In normal rats, parafascicular neurons exhibited low firing rates (3.88+/-0.80 spikes/s). Concerning the pattern, 59% of the units discharged irregularly and 41% exhibited bursty pattern. In rats with 6-hydroxydopamine lesions, the firing rate decreased significantly during the first week post-lesion (1.15+/-0.36 spikes/s, P<0.01). During the second week, the firing rate was slightly, but not significantly, lower (2.59+/-0.41 spikes/s, P>0.05) than that of normal rats to return to the basal level three weeks post-lesion (3. 66+/-0.41 spikes/s, P>0.05). In these three groups of 6-hydroxydopamine-lesioned rats, the firing pattern showed no change when compared to control animals. These results show that the lesion of nigral dopaminergic neurons induced a transient decrease of the firing rate of parafascicular neurons with no change in the firing pattern demonstrating the absence of a stable influence of the dopaminergic system on the spontaneous activity of parafascicular neurons.

Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal activities of the substantia nigra pars reticulata and ventrolateral nucleus of the thalamus in the rat.

Electrophysiological recordings were made in anaesthetized rats to investigate the mode of function of high-frequency stimulation of the subthalamic nucleus used as a therapeutic approach for Parkinson's disease. High-frequency electrical stimulation of the subthalamic nucleus (130 Hz) induced a net decrease in activity of all cells recorded around the site of stimulation in the subthalamic nucleus. It also caused an inhibition of the majority of neurons recorded in the substantia nigra pars reticulata in normal rats (94%) and in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (90%) or with ibotenic acid lesions of the globus pallidus (79.5%). The majority of cells recorded in the ventrolateral nucleus of the thalamus responded with an increase in their activity (84%). These results show that high-frequency stimulation of the subthalamic nucleus induces a reduction of the excitatory glutamatergic output from the subthalamic nucleus which results in deactivation of substantia nigra pars reticulata neurons. The reduction in tonic inhibitory drive of nigral neurons induces a disinhibition of activity in the ventrolateral motor thalamic nucleus, which should result in activation of the motor cortical system.

Implication of the subthalamic nucleus in the pathophysiology and pathogenesis of Parkinson's disease.

The subthalamic nucleus (STN) has been shown to play an important role in the control of movement and has been considered as a key structure in the functional organization of the basal ganglia. Several studies postulated that the STN plays a critical role in the pathophysiology of Parkinson's disease and that its inhibition or its lesioning can reverse the cardinal motor symptoms. Nevertheless, the beneficial effect was accompanied by dyskinetic abnormal movements. In order to avoid unpleasant and irreversible side effects we used high-frequency stimulation (HFS) of the STN instead of lesions. We have shown that parkinsonian motor symptoms, akinesia, rigidity, and tremor can be alleviated by HFS of the STN in the nonhuman primate model. Side effects were controllable and appeared only at intensities higher than that inducing the improvement of motor symptoms. In severe parkinsonian patients, bilateral STN-HFS greatly improved parkinsonian motor symptoms. Motor fluctuations were attenuated and patients became independent in most activities of daily living. It appears that STN-HFS mimics the effects of lesions by inhibiting its neuronal activity. In a rat model of parkinsonism, we studied the implication of the STN in the excitotoxicity of nigral dopamine cells. We showed that kainic acid lesioning of the STN can protect nigral dopaminergic cells against 6-hydroxydopamine-induced toxicity. The evidence reviewed in the present article clearly demonstrates that the STN is implicated in the pathophysiology and pathogenesis of Parkinson's disease.

Time-course of changes in firing rates and firing patterns of subthalamic nucleus neuronal activity after 6-OHDA-induced dopamine depletion in rats.

The subthalamic nucleus (STN) plays a key role in motor control. Disorganization of its neuronal activity is implicated in the manifestation of parkinsonian motor symptoms. The aim of the present work was to study the time-course of changes in the firing activity of STN neurons in a rat model of parkinsonism. Electrophysiological recordings were done in normal rats and four groups of rats at different time points after 6-hydroxydopamine (6-OHDA) microinjection into the pars compacta of substantia nigra (SNc). Results showed a significant decrease in firing rate during the first and second weeks post lesion (5.53+/-0.56 and 7.66+/-0.73 spikes/s, respectively) compared to normal rats (11.13+/-0.59 spikes/s). From the 3rd week after 6-OHDA injection the firing rates returned toward baseline, with an average of 9.71+/-0.51 spikes/s during the 3rd week and 11.13+/-0.71 spikes/s during the 4th week. With regard to firing pattern, the majority of STN cells (90%) discharged regularly or slightly irregularly in normal animals. Only 4% exhibited burst activity and 6% had mixed firing patterns. After SNc-lesion, the percentage of cells exhibiting burst and mixed patterns increased progressively from 35% during the first week to 56% at week 4 post-lesion. In sum, these experiments revealed that the firing rate of STN neurons was altered only transiently following nigral lesions, whereas a progressive and stable change in the firing pattern was observed up to 4 weeks post lesion, suggesting that the persistence of bursts firing more closely relates to the motor pathologies of this rat model of parkinsonism.

[Occurrence of Culex modestus inatomii Kamimura et Wada in Rongcheng city, Shandong Province].

A mosquito survey was made at Rongcheng City, Shandong Province in August, 1991. Altogether 4 genera and 8 species of mosquitoes were collected in this survey, namely Aedes dorsalis (Meigen), Anopheles sinensis Wiedemann, An. yatsushiroensis Miyazaki, Culex fuscanus Wiedemann, Cx. modestus inatomii Kamimura et Wada, Cx. pipiens pallens Coquillett, Cx. tritaeniorhynchus Giles and Mansonia uniformis (Theobald). Among them Cx. modestus inatomii and An. yatsushiroensis were found to be the first record for China and Shandong Province respectively. The morphology and taxonomic status of the above two species are discussed briefly.