Effects and mechanism of low frequency stimulation of pedunculopontine nucleus on spontaneous discharges of ventrolateral thalamic nucleus in rats / 生理学报

Parkinson's disease is a progressive neurodegenerative disorder characterized clinically by rigidity, akinesia, resting tremor and postural instability. It has recently been suggested that low frequency stimulation of the pedunculopontine nucleus (PPN) has a role in the therapy for Parkinsonism, particularly in gait disorder and postural instability. However, there is limited information about the mechanism of low frequency stimulation of the PPN on Parkinson's disease. The present study was to investigate the effect and mechanism of low frequency stimulation of the PPN on the firing rate of the ventrolateral thalamic nucleus (VL) in a rat model with unilateral 6-hydroxydopamine lesioning of the substantia nigra pars compacta. In vivo extracellular recording and microiontophoresis were adopted. The results showed that the firing rate of 60.71% VL neurons in normal rats and 59.57% VL neurons in 6-hydroxydopamine lesioned rats increased with low frequency stimulation of the PPN. Using microiontophoresis to VL neurons, we found the firing rate in VL neurons responded with either an increase or decrease in application of acetylcholine (ACh) in normal rats, whereas with a predominant decrease in M receptor antagonist atropine. Furthermore, the VL neurons were mainly inhibited by application of γ-aminobutyric acid (GABA) and excited by GABA(A) receptor antagonist bicuculline. Importantly, the VL neurons responding to ACh were also inhibited by application of GABA. We also found that the excitatory response of the VL neurons to the low frequency stimulation of the PPN was significantly reversed by microiontophoresis of atropine. These results demonstrate that cholinergic and GABAergic afferent nerve fibers may converge on the same VL neurons and they are involved in the effects of low frequency stimulation of the PPN, with ACh combining M(2) receptors on the presynaptic membrane of GABAergic afferents, which will inhibit the release of GABA in the VL and then improve the symptoms of Parkinson's disease.

Effects of unilateral lesion of the nigrostriatal pathway by 6-OHDA on the neuronal activities of the pedunculopontine nucleus and the ventrolateral thalamic nucleus / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes in neuronal activities of the pedunculopontine nucleus (PPN) and the ventrolateral thalamic nucleus (VL) after unilateral 6-hydroxydopamin (6-OHDA) lesioning of the striatum in rats.</p><p><b>METHODS</b>Extracellular single-unit recordings were perin normal rats and 6-OHDA lesioned rats to observe the firing rate and firing pattern occurring in PPN and VL neurons.</p><p><b>RESULTS</b>The firing rate of PPN neurones significantly increased from (8.31 +/- 0.62) Hz in normal rats to (10.70 +/- 0.85) Hz in 6-OHDA lesioned rats. The firing pattern changed towards more irregular and bursty when compared with the normal rats, with the firing rate increasing in regular pattern. The firing rate of VL neurones in normal rats and 6-OHDA lesioned rats were (6.25 +/- 0.54) Hz and (5.67 +/- 0.46)Hz respectively, whereas to normal animals. Surthere were no significant differences in these two groups. In addition, the firing pattern did not change in VL compared prisingly, the firing rate in burst pattern decreased significantly.</p><p><b>CONCLUSION</b>These findings demonstrate that PPN neurons are overactive in 6-OHDAlesioned rats, indicating the participation of this nucleus in the pathophysiology of parkinsonism and the activities of VL neurons might be regulated by projection from PPN to VL.</p>

Effect of stimulation of STN on the firing activities of the SNr neurons in rats / 中国应用生理学杂志

<p><b>AIM</b>To research the spontaneous firing activities during different-frequency stimulation of subthalamic nucleus and microelectrophoresis GABA, Glu and their antagons respectively, approaching the mechanism of DBS in the treatment of Parkinson's disease further.</p><p><b>METHODS</b>Using extracellular recording to investigate the effect of different-frequency stimulation of STN and microelectrophoresis several drugs on the spontaneous firing activities of the SNr neurons.</p><p><b>RESULTS</b>For STN stimulation at low frequency, there was no difference on the spontaneous firing activities of SNr neurons between pro-stimulation and meta-stimulation (P > 0.05). With the increasing of stimulation frequency, most of the SNr neurons were inhibited. While during the STN stimulation frequency at high-frequency, the firing rates of inhibited SNr neurons were changed (P < 0.05). Glu had catatonic excitement effect on the SNr neurons, whereas GABA had tonic inhibition effect. 80% of SNr neurons which were inhibited by STN-HFS were not inhibited by STN-HFS on the basis of excitatory effect of BIC.</p><p><b>CONCLUSION</b>To treat the motor symptoms of PD, when SIN is selected as the target nucleus, the electrical stimulation with high-frequency should be chosen. It is possible that SIN-HFS modulate the activity of SNr by inhibitory effect of GABA predominantly.</p>

The neuroprotective effects of lesion and high frequency stimulation of the subthalamic nucleus on the substantia nigra neurons / 中国应用生理学杂志

<p><b>AIM</b>To investigate the neuroprotective effects of lesion and high frequency stimulation(HFS) of the subthalamic nucleus (SIN) on the substantia nigra pars compacta(SNc) neurons and its probable mechanism.</p><p><b>METHODS</b>The PD models were induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequence stimulation to SIN and injection of ibotenic acid to STN on PD rats, the changes of behavior were observed. The substantia nigra neurons were detected by using special-dyeing, TUNEL techniques and immunohistochemistry methods.</p><p><b>RESULTS</b>In the stimulation group, the apoptotic rate was significantly lower than PD model group and lesion group (P < 0.05). Compared with normal rats, model group and lesion one had the similar results of expression of Bcl-2, Bax and their ratio, which were lower expression of Bcl-2, higher expression of Bax and the decrease of their ratio (P < 0.05). In the stimulation group, the expression of Bcl-2 and Bcl-2/Bax were much higher than model group and lesion group. The number of apoptotic neurons of rats in lesion group was smaller than model ones (P < 0.05), but there was no significant difference in expression of Bcl-2, Bax and their ratio (P > 0.05).</p><p><b>CONCLUSION</b>Lesion or HFS of STN have the neuroprotective effects on SNc neurons of PD rats, and HFS has a better long-term effect.</p>

Effects of electrical stimulation of the parafascicular nucleus on the neuronal activities of the subthalamic nucleus and the ventromedial nucleus in rats / 生理学报

The present study was designed to investigate the function and mechanism of high-frequency stimulation (HFS) of the parafascicular nucleus (PF) used as a therapeutic approach for Parkinson's disease (PD). PD rat model was built by injecting 6-hydroxydopamine (6-OHDA) into the substartia nigra pars compacta of adult male Sprague-Dawley rats. Using the ethological methods, we examined the effect of electrical stimulation of PF on the apomorphine-induced rotational behavior in PD rats. Moreover, Electrophysiological recordings were made in rats to investigate the effects of electrical stimulation of PF on the neuronal activities of the subthalamic nucleus (STN) and the ventromedial nucleus (VM). Our results showed that one week after HFS (130 Hz, 0.4 mA, 5 s) of PF, there was significant improvement in apomorphine-induced rotational behavior in PD rats. HFS of PF caused an inhibition of the majority of neurons (84%) recorded in the STN in PD rats. The majority of cells recorded in the VM of the thalamus responded to the HFS with an increase in their unitary discharge activity (81%). These effects were in a frequency-dependent manner. Only stimulus frequencies above 50 Hz were effective. Furthermore, employing microelectrophoresis, we demonstrated that glutamatergic and GABAergic afferent nerve fibers converged on the same STN neurons. These results show that the HFS of PF induces a reduction of the excitatory glutamatergic output from the PF which in turn results in deactivation of STN neurons. The reduction in tonic inhibitory drive from the basal ganglia induces a disinhibition of activity in the VM, a motor thalamic nucleus. In conclusion, the results suggest that HFS of PF may produce a therapeutic effect in PD rats, which is mediated by the nuclei of PF, STN and VM.

Effect of cortical spreading depression on spontaneous firing activities of STN neurons in rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the effect of cortical spreading depression (CSD) on the spontaneous firing activities of neurons of subthalamic nucleus (STN) in normal and model rat of Parkinson's disease (PD).</p><p><b>METHODS</b>Extracellular recording was used to research the neuronal electric activities in subthalamic neurons. The changes of the discharge rates of subthalamic neurons were observed in control and PD rats after intracortical microinjection of KCl solution.</p><p><b>RESULTS</b>The discharge rates of subthalamic neurons in control and PD rats were (9.78 +/- 0.71) Hz and (23.81 +/- 1.08) Hz, respectively. The discharge rate of PD rats was increased significantly when compared with those of the control rats and the percentage of neurons discharging in bursts was obviously higher than those of control rats (P < 0.01). After a long latent period secondary to intracortical injection of KCl solution, the discharge rates in both group of subthalamic neurons were decreased apparently, then recovered slowly.</p><p><b>CONCLUSION</b>The discharge rate and bursting pattern are increased in PD rats and these abnormal activities can be improved by cortical depression. This result indicates that the changes in cortical excitability may be one of the factors increasing the activity of STN in PD.</p>

Effect of high-frequency stimulation to subthalamic nucleus on STR neuronal firing rates in Parkinson disease rats / 中国应用生理学杂志

<p><b>AIM</b>To observe the change of STR neuronal firing rates with high frequency stimulation of subthalamic nucleus in PD rats.</p><p><b>METHODS</b>A model of Parkinson's disease was induced by unilateral administration of 6-hydroxydopamine into right substantia nigra in rats. After the high-frequency stimulation to STN, the spontaneous firing rates of STR on normal and PD rats were recorded by using extracellular recordings.</p><p><b>RESULTS</b>Stimulation caused a direct excited effect of STR neurons in normal rats whereas a excited and inhibited effect in PD rats. The inhibited effect was correlated with the stimulation period (r = 0.94).</p><p><b>CONCLUSION</b>Stimulation to STN may inhibit the spontaneous firing rates of STR neurons in PD rats. These results also give some clues that high-frequency stimulation to STN may be a effective therapy to the clinical treatment of Parkinson's disease.</p>