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Dyskinesia is Closely Associated with Synchronization of Theta Oscillatory Activity Between the substantia nigra pars reticulata and Motor Cortex in the Off L-dopa State in Rats

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Neuroscience Bulletin 2021年第3期37卷 323-338页

作者： Jiazhi Chen Qiang Wang Nanxiang Li Shujie Huang Min Li Junbin Cai Yuzheng Wang Huantao Wen Siyuan Lv Ning Wang Jinyan Wang Fei Luo Wangming Zhang The National Key Clinic Specialty The Engineering Technology Research Center of the Ministry of Education of ChinaGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationDepartment of NeurosurgeryZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China Movement Disorders and Neuromodulation Unit Department for NeurologyCharite´-University Medicine Berlin10117 BerlinGermany

Excessive theta(θ)frequency oscillation and synchronization in the basal ganglia(BG)has been reported in elderly parkinsonian patients and animal models of levodopa(L-dopa)-induced dyskinesia(LID),particularly theθoscillation recorded during periods when L-dopa is withdrawn(the off L-dopa state).To gain insight into processes underlying this activity,we explored the relationship between primary motor cortex(M1)oscillatory activity and BG output in LID.We recorded local field potentials in the substantia nigra pars reticulata(SNr)and M1 of awake,inattentive resting rats before and after L-dopa priming in Sham control,Parkinson disease model,and LID model groups.We found that chronic L-dopa increasedθsynchronization and information flow between the SNr and M1 in off L-dopa state LID rats,with a SNr-to-M1 flow directionality.Compared with the on state,θoscillational activity(θsynchronization and informationflow)during the off state were more closely associated with abnormal involuntary movements.Our findings indicate thatθoscillation in M1 may be consequent to abnormal synchronous discharges in the BG and support the notion that M1θoscillation may participate in the induction of dyskinesia.

关键词： Parkinson's disease Dyskinesia substantia nigra pars reticulata Primary motor cortex Synchronization

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DNA oxidative stress and secondary,remote impairment in rat substantia nigra pars reticulata with cerebral cortex infarction

DNA oxidative stress and secondary,remote impairment in rat ...

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第三届中日双边药理学和临床药理学学术会议

作者： HE Mei-Xia~(1,2) ZENG Jin-Sheng~2 YANG Bo~1 HUA Hai-Ying~1 YE Qi-Xia GE Shi-Wen~1 ZHU Jian-Li~1 (1.Department of Pharmacology,Henan Institute of Medical Sciences,Zhengzhou University,Zhengzhou 450052,China 2.Department of Neurology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China)

AIM To investigate the oxidative DNA dam- age within the substantia nigra pars reticulata (SNR) after focal cortical infarction,and explore the effects of ebselen on the oxidative DNA damage after cerebral cortex infarc- tion in hypertensive rats.METHODS Middle cerebral artery occlusion (MCAO) was induced in stroke-prone re- novascular hypertensive rats,and the rats were randomly divided into five groups:sham operation group,ischemia group,vehicle group and ebselen (10 and 30 mg·kg, ig) groups.Each group had five animals.Two weeks after the MCAO,the SNR from each group was sectioned and stained with hematoxylin-eosin (HE).Oxidative damage was determined by 8-hydroxy-2’-deoxyguanosine (8- ohdG) immunohistochemistry.RESULTS Two weeks after the MCAO,HE staining showed that MCAO resulted in the ipsilateral SNR brain cells damaged,exhibited the characteristic morphological features of damage,ie, shrinkage and triangulation of the nucleus and cytoplasm. Administration of ebselen 10 mg·kg slightly ameliorated the SNR damage,and 30 mg·kg obviously ameliorated the damage on HE-stained slices.Compared with vehicle group,increase in number of 8-ohdG positive cells (0.1 mm)was detected in ipsilateral SNR (127.4±17.9 vs 97.6±15.5,P＜0.05).Administration of ebselen at 10 or 30 mg·kg decreased the level of 8-ohdG (100.2± 17.9 and 98.2±15.2 vs 127.4±17.9,P＜0.05). CONCLUSION After two weeks,there is a marked increase of DNA oxidative stress,ebselen can obviously decrease DNA oxidative stress in SNR.

关键词： cerebral infarction substantia nigra pars reticulata 8-hydroxydeoxyguanosine rats

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Information integration role of internal segment of globus pallidus and substantia nigra pars reticulata in rats basal ganglia during exercise-induced fatigue

Information integration role of internal segment of globus p...

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中国神经科学学会第十届全国学术会议

作者： Li-Juan HOU Rong-Guang HU Xiao-Li LIU De-Cai QIAO Exercise physiology Laboratory Beijing Normal University Shanxi University of Finance and Economics

Objective Investigated internal segment of globus pallidus and substantia nigra pars reticulata’s electricity activity after exercise-induced fatigue,discuss the information integration role of GPi and SNr in rats basal ganglia to reveal the role of GPi and SNr in central mechanism of exercise-induced fatigue.Methods Using deep brain stimulation,glass microelectrode recording technique,and microinjection of drugs techniques to observe the signal of GPi and SNr dealing with information from indirect and direct pathway.Results The excitatory unit frequency of GPi and SNr evoked discharge increases by degrees within a certain range when the stimulus frequency increases;reaction of GPi and SNr neurons to different frequency stimulation in fatigue group rats are greater than control group rats;when the frequency of stimulation continues to increase,discharge frequencies of GPi and SNr neurons in both two group rats decrease.The proportion of GPi and SNr excitatory response unit in fatigue group is more than that in control group when the stimulus frequency doesn’t change;frequencies of SNr neurons in fatigue group are significantly higher than those in control group.After microinjection of KA,the proportion of inhibitory response unit in fatigue group is larger than that in control group.After microinjection of Fenoldopam,the proportion of SNr inhibitory response unit in fatigue group is larger than that in control group,and also larger than proportion of GPi inhibitory response unit in fatigue group;after microinjection of SCH23390,the proportion of excitatory response unit in fatigue group is larger than that in control group.Conclusion GPi and SNr neurons paly different function role in information integration in direct and indirect pathway.These two nuclei make consistent response to direct and indirect pathway under low level activities of direct and indirect pathway;but SNr neurons show more significant response under high level activities of direct and indirect pathway.While SNr neurons play a major role in the

关键词： exercise-induced fatigue internal segment of the globus pallidus substantia nigra pars reticulata deep brain stimulation microinjection

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Glutamatergic Neurons in the Caudal Zona Incerta Regulate Parkinsonian Motor Symptoms in Mice

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Neuroscience Bulletin 2022年第1期38卷 1-15页

作者： Li-Xuan Li Yu-Lan Li Jin-Tao Wu Ji-Zhou Song Xiao-Ming Li Department of Neurobiology and Department of Neurology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou310003China NHC and CAMS Key Laboratory of Medical Neurobiology Ministry of Education Frontier Science Center for Brain Research and Brain-Machine IntegrationSchool of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhou310030China Department of Engineering Mechanics Soft Matter Research Centerand Key Laboratory of Soft Machines and Smart Devices of Zhejiang ProvinceZhejiang UniversityHangzhou310063China

Parkinson’s disease(PD)is the second most common and fastest-growing neurodegenerative disorder.In recent years,it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis.However,little is known about whether and how the caudal zona incerta(ZIc)regulates parkinsonian motor symptoms.Here,we showed that specific glutamatergic but not GABAergic ZIc^(VgluT2) neurons regulated these symptoms.ZIc^(VgluT2) neuronal activation induced time-locked parkinsonian motor symptoms.In mouse models of PD,the ZIc^(VgluT2) neurons were hyperactive and inhibition of their activity ameliorated the motor deficits.ZIc^(VgluT2) neurons monosynaptically projected to the substantia nigra pars reticulata.Incerta-nigral circuit activation induced parkinsonian motor symptoms.Together,our findings provide a direct link between the ZIc,its glutamatergic neurons,and parkinsonian motor symptoms for the first time,help to better understand the mechanisms of PD,and supply a new important potential therapeutic target for PD.

关键词： Parkinson's disease Caudal zona incerta Glutamate substantia nigra pars reticulata Parkinsonian motor symptoms

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An inhibitory nigra-parafascicular pathway mediates the development of temporal lobe epilepsy

An inhibitory nigra-parafascicular pathway mediates the deve...

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中国神经科学学会第十二届全国学术会议

作者： Bin Chena Ying Wanga Cenglin Xua Yi Wang Heming Cheng Liying Chen Tingting Hu Junli Zhao Zhong Chen Department of Pharmacology Key Laboratory of Medical Neurobiology of the Ministry of Health of China School of Basic Medical Sciences College of Pharmaceutical Sciences Zhejiang University Epilepsy Center Second Affiliated Hospital School of Medicine Zhejiang University Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases First Affiliated Hospital School of Medicine Zhejiang University

The substantia nigra pars reticulata（SNr）, a region that mainly contains GABAergic neurons, is thought to be involved in epilepsy, but its precise cellular and neuronal circuitry mechanisms in temporal lobe epilepsy（TLE） have not been investigated. Using single-unit recordings and calcium fiber photometry, we found that SNr GABAergic/parvalbumin（PV） neurons were activated during seizures. Optogenetic and chemogenetic inhibition of SNr PV neurons retarded the development of TLE, whereas activation of these neurons promoted the development of TLE. In addition, epilepsy was bilaterally regulated by optogenetic manipulation of SNr PV projection fibers in the parafascicular nucleus（PF）, but not in the reticularis nucleus（RT） or the reuniens nucleus（RE）. Furthermore, in vivo/in vitro electrophysiology combined with rabies virus-assisted circuit-mapping, showed that SNr PV neurons directly project to PF GABAergic neurons. Finally, optogenetic manipulation of PF GABAergic neurons mimicked the role of PF-projecting PV fibers from the SNr in the development of TLE. Optogenetic activation of PF GABAergic neurons retarded the development of TLE, whereas inhibition of these neurons promoted the development of TLE. Collectively, our results revealed a previously unknown neural pathway, originating from SNr PV neurons to PF GABAergic neurons, involved in TLE. These findings are relevant for a better understanding of pathological network changes and might provide new insight for therapeutic manipulations in TLE.

关键词： temporal lobe epilepsy inhibitory neuronal circuit parvalbumin neurons substantia nigra pars reticulata parafascicular nucleus

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