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Off-line analysis of single-unit neuronal discharge in the globus pallidus region in Parkinson＇s disease

Chinese Medical Journal 2010年第14期123卷 1884-1887页

作者： ZHAO Ya-qun ZHOU Jing-an WANG Yong YU Jian-chen ZHANG Hui Department of Neurosurgery 309th Clinical Department of Chinese People's Liberation Army General Hospital Beijing 100091 China Institute of Biomedicine Xi'an Jiaotong University of China Xi'an 710054 China

Background The accuracy of microelectrode-guided localization can make the operation safe and effective, but only experienced neurosurgeons are capable of performing this operation. A good index to identify neuronal discharges between globus pallidus interna and globus pallidus externa is needed. The aim of this research was to establish a good and practical electrophysiologic index to distinguish neuronal discharge in the interior globus pallidus from neuronal discharge in the exterior globus pallidus region of the brain in Parkinson＇s disease. The effect of neurons having an atypical discharge on successful surgical localization was also quantitatively evaluated Methods The study included 30 patients with primary Parkinson＇s disease who underwent pallidotomy between September 2000 and October 2002. During each pallidotomy, the neuronal discharges in the pallidum and its vicinity were recorded. The recorded spikes were used to calculate the frequency, burst index, pause index, and pause ratio of the single-unit discharge. The interior and exterior globus pallidus regions were compared in terms of frequency, burst index, pause index, and pause ratio. The sensitivity, specificity, false-negative ratio, false-positive ratio, and accuracy of those indices were then evaluated. Results The values of frequency, burst index, pause index, and pause ratio in the interior globus pallidus were （96±43） Hz, 2.31±1.81, 0.05±0.05, and 0.27±0.28, respectively, and in the exterior globus pallidus were （59±27） Hz, 0.88±0.63, 0.20±0.14, and 1.54±1.17, respectively. Use of the four indices to distinguish the two neuron types produced a sensitivity of 0.84, 0.78, 0.77, and 0.93 with a specificity of 0.64, 0.79, 0.88, and 0.87, respectively. The false-positive ratio was 0.36, 0.21, 0.12, and 0.13 and the false-negative ratio was 0.16, 0.22, 0.23, and 0.07 while the accuracy was 0.72, 0.79, 0.80, and 0.90, respectively. Conclusions Pause ratio is a relatively reliable index to distinguish neuronal discharges between the interior and ex

关键词： Parkinson＇s disease globus pallidus neural discharge intraoperative localization comparative study

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Modulation of firing activity by endogenous GABA_A receptors in the globus pallidus of MPTP-treated parkinsonian mice

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Neuroscience Bulletin 2013年第6期29卷 701-707页

作者： Xin-Yi Chen Yan Xue Hua Wang Su-Hong Zhu Xiao-Meng Hao Lei Chen Clinical Medicine 2009 Shandong University Medical School Department of Physiology Qingdao University Department of Physiology Binzhou Medical College

The globus pallidus in rodents,equivalent to the external segment of the globus pallidus in primates,plays an important role in movement regulation.Previous studies have shown abundant γ-aminobutyric acid（GABA）ergic innervation and GABAA receptors in the globus pallidus.In this study,we investigated the effects of endogenous GABAA receptors on the spontaneous firing activity of pallidal neurons in both normal and MPTP-treated mice using multi-barrel electrodes extracellular recordings in vivo.We found that in normal mice,pressure ejection of 0.1 mmol/L gabazine,a specific GABA A receptor antagonist,increased the spontaneous firing rate of globus pallidus neurons by 27.6 ± 5.6%.Furthermore,in MPTP mice（14 days after MPTP treatment）,0.1 mmol/L gabazine increased the firing rates by 51.0 ± 7.9%,significantly greater than in normal mice.These results suggest that endogenous GABAA receptors modulate the activity of globus pallidus neurons.The present findings may provide a rationale for investigations into the potential role of GABAA receptors in Parkinson’s disease.

关键词： globus pallidus GABA A receptor Parkinson’s disease single unit recording

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Atlas of the Striatum and globus pallidus in the Tree Shrew: Comparison with Rat and Mouse

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Neuroscience Bulletin 2018年第3期34卷 405-418页

作者： Rong-Jun Ni Zhao-Huan Huang Yu-Mian Shu Yu Wang Tao Li Jiang-Ning Zhou Psychiatric Laboratory and Mental Health Center West China Hospital of Sichuan University Chinese Academy of Science Key Laboratory of Brain Function and Diseases School of Life Sciences University of Science and Technology of China Huaxi Brain Research Center West China Hospital of Sichuan University School of Architecture and Civil Engineering Chengdu University

The striatum and globus pallidus are principal nuclei of the basal ganglia. Nissl-and acetylcholinesterasestained sections of the tree shrew brain showed the neuroanatomical features of the caudate nucleus（Cd）,internal capsule（ic）, putamen（Pu）, accumbens, internal globus pallidus, and external globus pallidus. The ic separated the dorsal striatum into the Cd and Pu in the tree shrew, but not in rats and mice. In addition, computerbased 3 D images allowed a better understanding of the position and orientation of these structures. These data provided a large-scale atlas of the striatum and globus pallidus in the coronal, sagittal, and horizontal planes, the first detailed distribution of parvalbumin-immunoreactive cells in the tree shrew, and the differences in morphological characteristics and density of parvalbumin-immunoreactive neurons between tree shrew and rat. Our findings support the tree shrew as a potential model for human striatal disorders.

关键词： Striatum globus pallidus Basal ganglia Reconstruction Rodent Parvalbumin

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Apelin-13 regulates electrical activity in the globus pallidus and induces postural changes in rats

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Neural Regeneration Research 2021年第11期16卷 2264-2268页

作者： Ying Wang Yan Xue Cui Liu Lei Chen Department of Physiology School of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina

The globus pallidus is the relay nucleus of the basal ganglia,and changes in its electrical activity can cause motor impairment.Apelin-13 is widely distributed in the central and peripheral nervous systems.It has been demonstrated that apelin-13 plays important roles in the regulation of blood pressure and other non-motor functions.However,its role in motor function has rarely been reported.In the present study,apelin-13(10μM/100μM)was injected into the globus pallidus of rats.The results showed that apelin-13 increased the spontaneous discharges in the majority of pallidal neurons.However,an apelin-13-induced inhibitory effect on the firing rate was also observed in a few pallidal neurons.In postural tests,after the systemic administration of haloperidol,unilateral pallidal injection of apelin-13 caused a contralateral deflection.Together,these findings suggest that apelin-13 regulates the electrical activity of pallidal neurons and thus participates in central motor control in rats.The study was approved by the Animal Ethics Committee of Qingdao University(approval No.20200615Wistar0451003020)on June 15,2020.

关键词： apelin-13 basal ganglion electrophysiology firing rate globus pallidus microinjection motor behavior movement disorder

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Neuronal firing in the globus pallidus internus and the ventrolateral thalamus related to parkinsonian motor symptoms

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Chinese Medical Journal 2009年第19期122卷 2308-2314页

作者： CHEN Hai ZHUANG Ping ZHANG Yu-qing LI Jian-yu LI Yong-jie Beijing Institute of Functional Neurosurgery Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China

Background It has been proposed that parkinsonian motor signs result from hyperactivity in the output nucleus of the basal ganglia, which suppress the motor thalamus and cortical areas. This study aimed to explore the neuronal activity in the globus pallidus internus （GPi） and the ventrolateral thalamic nuclear group （ventral oral posterior/ventral intermediate, Vop/Vim） in patients with Parkinson＇s disease （PD）. Methods Twenty patients with PD who underwent neurosurgery were studied. Microelectrode recording was performed in the GPi （n=10） and the Vop/Vim （n=10） intraoperatively. Electromyography （EMG） contralateral to the surgery was simultaneously performed. Single unit analysis was carried out. The interspike intervals （ISI） and coefficient of variation （CV） of ISI were calculated. Histograms of ISI were constructed. A unified Parkinson＇s disease rating scale （UPDRS） was used to assess the clinical outcome of surgery. Results Three hundred and sixty-three neurons were obtained from 20 trajectories. Of 175 GPi neurons, there were 15.4% with tremor frequency, 69.2% with tonic firing, and 15.4% with irregular discharge. Of 188 thalamic neurons, there were 46.8% with tremor frequency, 22.9% with tonic firing, and 30.3% with irregular discharge. The numbers of three patterns of neuron in GPi and Vop/Vim were significantly different （P 〈0.001）. ISI analysis revealed that mean firing rate of the three patterns of GPi neurons was （80.9±63.9） Hz （n=78）, which was higher than similar neurons with 62.9 Hz in a normal primate. For the Vop/Vim group, ISI revealed that mean firing rate of the three patterns of neurons （n=95） was （23.2±17.1） Hz which was lower than similar neurons with 30 Hz in the motor thalamus of normal primates. UPDRS indicated that the clinical outcome of pallidotomy was （64.3±29.5）%, （83.4±19.1）% and （63.4±36.3）%, and clinical outcome of thalamotomy was （92.2±12.9）%, （68.0±25.2）% and （44.3±7.2）% for tremor, rigidity and bradykinesia, respectively. A significant difference of tremor and rigidity was fo

关键词： Parkinson＇s disease movement disorders globus pallidus thalamus microelectrodes

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Effects of dopamine D1 receptor on the firing of globus pallidus neurons in normal rats

Effects of dopamine D1 receptor on the firing of globus pall...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Rui QI,Lei CHEN~* Department of Physiology,Qingdao University,Qingdao 266071,China

The globus pallidus in rodents,equivalent to the external globus pallidus in primates,plays an important role in movement regulation.Morphological studies have shown that the globus pallidus receives dopamine innervation from the collaterals of nigrostriatal fibers.Early electrophysiological study has shown that systemic administration of D receptor agonist SKF38393 increased the spontaneous firing in normal rats.Intrapallidal microinjection of dopamine partially restores motor deficits in 6-OHDA parkinsonian rat model.In the present study,we employed extracellular single unit recordings to study the effects of dopamine D receptor agonist SKF38393 in the globus pallidus of normal rats.In 25 out of 58 globus pallidus neurons,micro-pressure injection of 5 mmol/L SKF38393 increased the frequency of spontaneous firing rate from(9.8±1.9) Hz to(14.3±2.5) Hz.The average increase was 61.5%±8.3%(Pglobus pallidus neurons,micro-pressure injection of 5 mmol/L SKF38393 decreased the frequency of spontaneous firing rate from(4.7±1.2) Hz to(2.1±0.6) Hz.The average decrease was 52.1%±6.7%(Pglobus pallidus neurons.The present findings may provide a rational reason for further investigations into the potential of pallidal dopamine D receptor in the treatment of Parkinson’s disease.

关键词： globus pallidus dopamine single unit recording

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Electrophysiological effects of groupⅠmetabotropic glutamate receptors on globus pallidus neurons in normal and parkinsonian rats

Electrophysiological effects of groupⅠmetabotropic glutamat...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Xiang-Rong SUN,Lei CHEN~* Department of Physiology,Faculty of Medicine,Qingdao University,Qingdao,266071 China

＜正＞Objective The globus pallidus plays a critical role in movement regulation.Morphological studies have shown that group I mGluRs（both mGluR1 and mGluR5） are strongly expressed in the globus pallidus.These receptors have also been implicated as therapeutic targets for Parkinson’s disease.Up to now,little is known about the electrophysiological effects of activating group I mGluRs on the globus pallidus neurons in vivo.The aim of the present study was to investigate the effects of（R,S）-3,5-Dihydroxyphenylglycine（DHPG）,a selective agonist of group I mGluRs,on the firing rate of globus pallidus neurons in normal and 6-hydroxydopamine（6-OHDA） lesioned parkinsonian rats.Methods Single unit extracellular recording was used in this study.Results（1） Micropressure ejection of DHPG increased the spontaneous firing rate of globus pallidus neurons by 64.8%in normal rats.（2） Micropressure ejection of LY367385（antagonist of mGluR1） or MPEP（antagonist of mGluR5） alone had no effect on the firing rate of globus pallidus neurons.Furthermore, the excitatory effects of DHPG could be blocked by LY367385 but could not be blocked by MPEP.（3） In 6-OHDA lesioned parkinsonian rats,DHPG increased the spontaneous firing rate of globus pallidus neurons by 40.3%on the unlesioned side,but had no significant effect on the lesioned side.Conclusion Group I mGluRs produces excitatory effects on globus pallidus neurons via mGluR1.The activity of pallidal group I mGluRs may be decreased under parkinsonian state.This finding may provide a rationale for further investigations into the potential of pallidal mGluRs system in the pathogenesis and treatment of Parkinson’s disease.

关键词： group I mGluRs single unit recording DHPG MPEP LY367385 globus pallidus Parkinson’s disease

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Substance P excites globus pallidus neurons in vivo

Substance P excites globus pallidus neurons in vivo

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Qiao-Ling CUI~1,Wing-Ho YUNG~2,Lei CHEN~(1*) 1 Department of Physiology,Qingdao University,Qingdao 266071,China 2 Department of Physiology,The Chinese University of Hong Kong,Hong Kong,China

＜正＞The globus pallidus occupies a critical position in the indirect pathway of the basal ganglia.By innervating all the other basal ganglia nuclei,the globus pallidus plays an important role in normal movement regulation and in the pathophysiology of basal ganglia disorders.Substance P is a member of neurokinin family.Previous studies have reported the existence of substance P and its high affinity receptor,neurokinin-1 receptor,in globus pallidus.However,the function of substance P in globus pallidus is not well known.In the present study,we employed both in vivo extracellular recordings and behavioral test to study the effects of substance P in globus pallidus of rats.Micro-pressure ejection of selective neurokinin-1 receptor agonist,[Sar9,Met（02）l 1]substance P（SMSP）,increased the spontaneous firing rate of pallidal neurons in a concentration-dependent pattern,with the increase at 27.3%（0.01 mmol/L）,33.4%（0.03 mmol/L）, 45.5%（0.1 mmol/L）,38.4%（0.3 mmol/L） and 36.4%（1.0 mmol/L）,respectively.The selective neurokinin-1 receptor antagonist, SR140333B,prevented the excitatory effects induced by SMSP.After lesioning cholinergic neurons in globus pallidus by 192 IgG-saporin,0.1 mmol/L SMSP still increased the firing rate of pallidal neurons by 42.5%,which was not statistically different from that without 192 IgG-saporin treatment.In the behaving rats,we observed the postural effects of neurokinin- 1 receptor activation in globus pallidus.Consistent with electrophysiological results,unilateral microinjection of SMSP （0.1 mmol/L） led to a SR140333B sensitive contralateral deflection in the presence of systemic haloperidol administration. Further electrophysiological recordings showed that 0.1 mM SMSP increased the firing rate（49%） of pallidal neurons of rats with haloperidol administration,which was not different from that without haloperidol administration.Combining both electrophysiological and behavioral findings,we concluded that substance P produces excitatory effects on globus pallidus neurons via neurokinin-1 rec

关键词： globus pallidus substance P single unit recording

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Update on deep brain stimulation in Parkinson’s disease

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Translational Neurodegeneration 2015年第1期4卷 84-91页

作者： Daniel Martinez-Ramirez Wei Hu Alberto R.Bona Michael S.Okun Aparna Wagle Shukla Department of Neurology University of FloridaCollege of MedicineCenter for Movement Disorders and Neurorestoration3450 Hull RoadGainesvilleFL 32607USA Department of Neurosurgery Psychiatryand HistoryUniversity of FloridaCollege of MedicineCenter for Movement Disorders and NeurorestorationGainesvilleFL 32610USA

Deep brain stimulation(DBS)is considered a safe and well tolerated surgical procedure to alleviate Parkinson’s disease(PD)and other movement disorders symptoms along with some psychiatric conditions.Over the last few decades DBS has been shown to provide remarkable therapeutic effect on carefully selected patients.Although its precise mechanism of action is still unknown,DBS improves motor functions and therefore quality of life.To date,two main targets have emerged in PD patients:the globus pallidus pars interna and the subthalamic nucleus.Two other targets,the ventralis intermedius and zona incerta have also been selectively used,especially in tremor-dominant PD patients.The main indications for PD DBS have traditionally been motor fluctuations,debilitating medication induced dyskinesias,unpredictable“off time”state,and medication refractory tremor.Medication refractory tremor and intolerable dyskinesia are potential palliative indications.Besides aforementioned targets,the brainstem pedunculopontine nucleus(PPN)is under investigation for the treatment of ON-state freezing of gait and postural instability.In this article,we will review the most recent literature on DBS therapy for PD,including cutting-edge advances and data supporting the role of DBS in advanced neural-network modulation.

关键词： Movement disorders Subthalamic nucleus globus pallidus Neural network Brain modulation Closed-loop

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Deep brain stimulation for dystonia

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Translational Neurodegeneration 2014年第1期3卷 6-10页

作者： Wei Hu Matt Stead Department of Neurology Mayo Clinic College of Medicine200 First Street SWRochesterMN 55901USA

Deep brain stimulation(DBS)is an effective surgical treatment for medication-refractory movement disorders,and has been approved by the United States Food and Drug Administration for treatment of dystonia.The success of DBS in the treatment of dystonia depends on our understanding of the anatomy and physiology of this disorder and close collaboration between neurosurgeons,neurologists,clinical neurophysiologists,neuroradiologists and neuropsychologists.Currently,pallidal DBS is an established treatment option for medically refractive dystonia.This review is intended to provide a comprehensive review of the use of DBS for dystonia,focusing mainly on the surgical aspects,clinical outcome,MRI findings and side effects of DBS.

关键词： Dystonia Deep brain stimulation Surgical outcomes Neuromodulation globus pallidus

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