帕金森病患者丘脑腹外侧核超微结构观察

利用透射电镜对１６例帕金森病患者丘脑腹外侧核活检组织进行了超微结构观察，结果发现：神经细胞数量减少，胞体变小，核呈浓缩变形，线粒体肿胀变性，嵴突短小或消失。突触末梢水肿，扩大呈空泡样，突触小泡数量减少或消失。星形胶质细胞水肿，膜性细胞器破坏。毛细血管内皮细胞肿胀，管腔狭窄，线粒体肿胀变性。病变随患者病情加重而变化明显。结果提示丘脑腹外侧核超微结构上的改变有可能成为临床判断病变程度的辅助诊断指标。     

猫丘脑腹后外侧核内皮质—丘脑纤维终末与丘脑—皮质投射神经元…

用ＣＢ－ＨＲＰ逆行追踪与顺行溃变相结合的方法，对猫丘脑腹后外侧核内的来自大脑皮质体感Ｉ区的皮质－丘脑纤维终末与丘脑－皮质投射神经元之间的突触连接进行了电镜观察。向猫大脑皮质体感Ｉ区内注射ＣＢ－ＨＲＰ５ｈ后，电解损毁原注射部位，术后动物存活４ｄ。电镜下发现丘脑腹后外侧核内存在５种突触连接方式：（１）溃变的轴突终末与ＨＲＰ标记神经元胞体形成轴－体突触；（２）溃变的轴突终末与ＨＲＰ标记的树突形成轴－树突     

猫丘脑腹后内侧核的超微结构及突触联系

在电镜下对猫丘脑腹后内侧核内的超微结构及突触联系进行观察。该核内的轴突终末主要有３种类型：（１）含有圆形小泡的小轴突终末；（２）含有圆形小泡的大轴突终末；（３）含有扁平小泡的突终末。该核内的树突主要为不含突触小泡的Ⅰ型树突，此外还可见到少量含有突触小泡的Ⅱ型树突。     

猫丘脑中央外侧核内丘脑皮质投射神经元的形态与分布

应用ＨＲＰ逆行追踪法在光镜水平研究了猫丘脑中央外侧核向前乙状回，前上薛氏回前端揣射的神经元的形态与分布。结果表明：中央外侧核向大脑皮质的投身为同侧投射，中央外侧核向前乙状回投射的神经元集中于核的尾段，少部分位于中段，偏内侧分布，大中，小，型投射神经元均有，以中，小型为主。     

大鼠丘脑下部至外侧隔核的投射

本文用HRP逆行追踪法研究20例大白鼠丘脑下部至外侧隔核的投射关系。结果表明,乳头体上核:乳头体外侧核、丘脑下部背内侧核、丘脑下部腹内侧核、丘脑下部前区、丘脑下部外侧区投射至同侧外侧隔核;弓状核亦发少量纤维至同侧外侧隔核。     

猫丘脑腹后外侧核内皮质—丘脑纤维终末与丘脑—皮质投射神经元之间的突触连接

用ＣＢ－ＨＲＰ逆行追踪与顺行溃变相结合的方法，对描丘脑腹后外侧核内的来自大脑皮质体感Ⅰ区的皮质—丘脑纤维终末与丘脑—皮质投射神经元之间的突触连接进行了电镜观察。向猫大脑皮质体感Ⅰ区内注射ＣＢ－ＨＲＰ５ｈ后，电解损毁原注射部位，术后动物存活４ｄ。电镜下发现丘脑瓜后外侧核内存在５种突触连接方式；（１）溃变的轴突终未与ＨＲＰ标记神经元胞体形成轴－体突触；（２）溃变的轴突终末与ＨＲＰ标记的树突形成轴—树突触；（３）溃变的轴突终末和其它突触前成分共同与中央树突形成汇聚型的突触复合体；（４）溃变的轴突终末与未标记树突形成的轴—树突触；（５）正常的轴突终末与ＨＲＰ标记神经元形成对称型的轴—体突触。     

大鼠孤束核向丘脑腹后内侧核及下丘脑外侧区的直接投射——HRP法研究

将30～50%HRP导入20例实验动物一侧的丘脑腹后内侧核和10例实验动物的一侧的下丘脑外侧区。标记细胞出现在双侧孤束核上、中、下三段,但以注射同侧多见,中、下段标记细胞出现数量较多,上段较少。标记细胞在孤束核各亚核的分布也不相同,在内侧亚核、连合亚核内较为密集。标记细胞以中、小型为主,偶见大型,多为梭形,亦可见多角形,标记细胞有1-2个突起且可见分叉;标记细胞直径为15～25μm,本文证实了孤束核的中、下段向丘脑腹后内侧核及下丘脑外侧区存在着直接的上行投射,并推测该投射可能是传导一般内脏感觉(包括内脏痛)的上行通路之一。本文还结合文献对体壁传入与内脏传入神经元在孤束核以上的高位中枢内的汇聚及其意义进行了讨论。     

猫丘脑腹后核内的树—树突触

在电镜下对猫丘脑核内的树－树突触进行了观察，树－树突触由含有少量突触小泡的Ⅱ型树突作为这估触前树突与Ⅰ型树突所构成。在树－树突触的突触前，后膜上可见厚度大致相同的致密物质沉着，为对称性突触。在丘脑腹后术 不这首次发现了交互性树－树这突触。     

猫丘脑中央外侧核内丘脑皮质投射神经元的超微结构及其突触联系

应用ＨＲＰ逆行追踪法在电镜水平上对猫丘脑中央外侧核内皮质投射神经元的超微结构及其突触联系首次进行了研究。该核内皮质投射神经元以中型多见，胞核较大，核仁清晰，偏位，核膜有凹陷，常染色质较多，胞质内含丰富的线粒体，游离核糖体和粗面内质网。标记树突直径变化较大，从０．６８μｍ到４．４μｍ，含较多的线粒体、微管及滑面内质网，凶突触小泡。标记的皮质投射神经元胞体和树突做为突触后成分，与非标记的突触前成分形成     

苍白球功能变化与帕金森症

As an important nucleus of basal ganglia, globus pallidus was concerned to involve in the neural mechanism of Parkinss disease (PD). Previous studies of PD patients and animal model indicate that neurotransmitters and receptors are changed in globus pallidus neurons, the balance between inhibition and excitation is broken in the output nuclei of basal ganglia, and globus pallidus neurons display bursting and oscillatory discharge, the synchronous tendency of neighboring neurons enhances. These neurophysiological changes are associated with PD symptoms, such as bradykinesia, rigidity and tremor, which reflects that globus pallidus plays an important role in the process of PD. In the present paper, the recent advances in pathophysiology in globus pallidus, its clinical application in treatment of Parkinsons disease, and the study direction in the future are reviewed.     

脑电近似熵分析对帕金森病患者认知功能障碍的评估作用

目的：观察帕金森病（PD）患者与对照者的脑电近似熵的差异,并探讨其对PD认知功能障碍的评估作用。方法：对31例PD患者和31例对照组进行简易精神状态检查量表（MMsE）测试、蒙特利尔认知评估量表（MoCA）测试、事件相关电位（ERP）检测P300波潜伏期（P3PL）,采集安静闭眼、闭眼心算、安静睁眼三种状态下的脑电信号,利用非线性参数近似熵对脑电数据进行分析。结果：①与对照组相比,PD组MMSE评分和MoCA评分均降低,P3PL延长,差异有统计学意义;②与对照组相比,在安静闭眼、闭眼心算、安静睁眼三种状态下,PD组的近似熵在大部分脑区降低,差异有统计学意义这些脑区在安静闭眼状态时是Fp1、Fp2、F4、O2、F8、T3、T4、T5、T6,在闭眼心算状态时是Fp1、F3、F4、C3、P3、O1、T3、T5、T6,在安静睁眼状态时除C4外的15个脑区;③与对照组相比,PD患者近似熵变化值于F3、C3、P3、O1降低,差异有统计学意义;④所有受试者安静闭眼、闭眼心算、安静睁眼三种状态下大部分脑区近似熵值与MMSE评分、MoCA评分呈正相关,与P3PL呈负相关。结论：脑电近似熵可以作为一项客观评定PD患者认知功能障碍的电生理指标。     

The primate globus pallidus: neuronal activity related to direction of movement

Summary Neurons in the arm areas of the external and internal segments of the globus pallidus (GPe and GPi) and the ventral pallidum (VP) have been examined in a visuomotor step-tracking task. This task, which was similar to that used previously to examine neurons in the arm area of the putamen, dissociated the direction of movement from the pattern of muscle activity associated with the movement. The major finding of the present study is that, as in the putamen, the activity of almost half of the neurons in GPe and GPi was related to the direction of movement. Cells with overall patterns of activity similar to muscle were rare, although many neurons had static and/or dynamic load effects which resembled those seen in muscle. Responses of neurons to load application have also been examined in this paradigm in order to determine the nature of possible somatosensory input. Short-latency sensory responses to load application were found in pallidum as previously in putamen, but, by contrast, they occurred somewhat later and included bidirectional responses. Similar proportions of cells in GP and putamen were related to static loads. Some VP neurons appeared to encode information about specific features of the trials, but the majority of responses were nonspecific suggesting relations to more general features of the task.This work was supported by grants from the U.S. Public Health Service (NIH NS15417 and NIH NS20471)     

帕金森病运动诱发电位及其影响因素的研究

目的：从运动功能、电生理检测方面观察帕金森病（PD）患者的皮质兴奋性的改变及其影响因素。方法：共68例PD患者,另选择30名健康者为对照组。采用统一帕金森病评定量表（UP-DRS）、经颅磁刺激运动诱发电位（MEP）作为评定指标。结果：PD患者MEP的静息阈值（RMT）、中枢传导时间（CMCT）较正常对照组明显降低或缩短,而波幅（Amp）则无明显差异。〉5年患者的RMT（40．70±4．74）,比≤5年患者的RMT（42．60±4．61）缩短;强直型患者的RMT（40．92±5．28）,比震颤型患者的RMT（42．93±3．97）缩短,差异有统计学意义。结论：PD患者存在运动功能障碍,大脑皮质兴奋性升高;强直型和病程长的患者病情较重,大脑皮质兴奋性升高更明显。     

帕金森病患者脑干听觉诱发电位的研究

目的：探讨帕金森病（PD）患者脑干听觉诱发电位（BAEP）表现及其对PD的诊断意义。方法：PD组患者67例,并选择年龄、性别与之相匹配的30例正常人为正常对照,观察两组BAEP的差异。比较PD患者不同病程、统一帕金森病评定量表（UPDRS）的不同评分、Hoehn—Yahr（H—Y）的不同分期的BAEP的异同。结果：PD患者BAEP总异常率为23．9％,以Ⅰ-Ⅲ波间期（IPL）异常为主。PD组患者Ⅲ波、V波潜伏期（PL）、Ⅰ-ⅢIPL、Ⅲ-ⅤIPL、Ⅰ—ⅤIPL较对照组明显延长,差异具有统计学意义。而在PD组中,病程≥5年的患者Ⅰ—ⅤIPL较病程〈5年的患者明显延长,UPDRS得分≥36分的患者波ⅢPL较UPDRS得分％36分的患者明显延长,差异具有统计学意义。而不同H—Y分期患者BAEP比较,差异无统计学意义。结论：PD患者听觉传导通路存在异常,随着病程延长,UPDRS评分增高,BAEP更容易出现异常。     

A quantitative analysis of pallidal discharge during targeted reaching movement in the monkey

Summary Neurons in the globus pallidus have been studied during reaching movements of the arm made at varying speeds. The reaching task is similar to one used in earlier experiments, in which disruption of normal pallidal output caused changes in movement time. The pallidal cells studied were those that showed task-related changes in activity and a modification of discharge when the arm was manipulated outside of the task. Neuronal discharge was assessed to evaluate two possible models, one in which the timing of task-related discharge varied as a function of movement time and the other in which the amplitude (mean firing rate) of the change in discharge varied as movement time varied. The relation between neuronal discharge and movement time was examined quantitatively on a trial-by-trial basis using a statistical algorithm that identified each phase of the change in neuronal discharge on each trial. A nonparametric statistic was used to determine the correlation between movement time and the duration or latency of changes in neural firing or the mean discharge during each phase of the cell's response. For fifty-five percent of the 40 neurons studied, the timing of the cell's response (duration or latency) varied as a function of movement time. For only 10 cells (25%) was there a significant correlation between movement time and the mean firing rate during one or more phases of the cell's response. Both timing and frequency modulation with movement time were limited to cells responsive to manipulation at the wrist or the shoulder.     

A quantitative comparison of basal ganglia neuronal activities of normal and Parkinson's disease model rats

The purpose of this study was to identify consistent characteristic changes of neuronal activity in basal ganglia (BG) nuclei associated with Parkinson's disease (PD) so that a reliable index of PD can be derived. A simple algorithm for automatic identification of firing patterns was devised as an essential tool to achieve this goal. A detailed quantitative analysis of firing patterns as well as firing rate was performed in three BG nuclei: the subthalamic nucleus (STN), the substantia nigra pars reticulate (SNpr), and the globus pallidus (GP). The results showed that the firing rate of STN neurons was not significantly altered in PD model rats. We also did not find a significant alteration in firing rates in the SNpr and GP between normal and PD model rats. In contrast, consistent changes of firing patterns were observed in all three BG nuclei in that the percentage of neurons with a regular firing pattern decreased whereas those with irregular, mixed, or burst patterns increased. This enables a simple algorithm based on burst detection and the shape of the interspike interval histogram to identify whether the neuronal activity is from normal or PD model rats.     

Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease

Current models of basal ganglia function suggest that some manifestations of Parkinson disease (PD) arise from abnormal activity and decreased selectivity of neurons in the subthalamic nucleus (STN) and globus pallidus internus (Gpi). Our goal was to examine the timing and direction selectivity of neuronal activity relative to visually guided movements in the STN and Gpi of patients with PD. Recordings were made from 152 neurons in the STN and 33 neurons in the Gpi of awake subjects undergoing surgery for PD. Corresponding EMG data were obtained for half the cells. We employed a structured behavioral task in which the subjects used a joystick to guide a cursor to one of four targets displayed on a monitor. Each direction was tested over multiple trials. Movement-related modulation of STN activity began on average 264±10 ms before movement initiation and 92±13 ms before initial EMG activity, while modulation of Gpi activity began 204±21 ms before overt movement initiation. In the STN, 40% of cells demonstrated perimovement activity, and of these 64% were directionally selective. In Gpi, 45% of cells showed perimovement activity of which 80% were selective. In both nuclei, directionally selective cells had significantly lower baseline firing rates than nonselective cells (41±5 vs 59±4 spikes/s in STN, and 50±9 vs 74±15 spikes/s in Gpi). These results suggest that STN activity occurs earlier than previously reported, and that higher neuronal firing rates maybe associated with decreased direction selectivity in PD patients.     

老年帕金森病患者事件相关电位检测与认知功能障碍的临床研究

目的：探讨老年帕金森病（PD）患者事件相关电位（ERP）与认知功能障碍的关系,并对其相关因素进行分析。方法：PD患者45例,根据年龄分组,≥60岁为PD老年组,〈60岁为PD非老年组。对所有入选患者进行ERP检测和韦氏成人智力量表中国修订版（WAIS-RC）检查,测定患者的ERP的N2、P3波潜伏期、波幅和患者的语言智商（VIQ）、操作智商（PIQ）、全智商（FIQ）等。结果：老年组PD患者ERP的N2、P3波潜伏期的异常率为73％,非老年组PD患者相应为33％,二者比较差异有极显著意义（P〈0．001）;老年组PD患者WAIS-RC测试异常率为60％,非老年组PD患者为20％,二者比较差异有统计学意义（P〈0．05）。患者的病程、受教育年限、运动功能障碍程度与ERP异常无相关性（P〉0．05）;病程与患者的VIQ、PIQ、FIQ无相关性（P〉0．05）;运动功能障碍程度与VIQ、PIQ、FIQ呈负相关（P〈0．05）;受教育年限与VIQ、PIQ、FIQ呈正相关（P〈0．05）。结论：老年组PD患者的认知功能障碍异常率明显高于非老年组PD患者。PD患者的认知功能障碍（VIQ、PIQ、FIQ）不仅与年龄有关,而且与运动功能障碍程度、受教育年限相关。ERP的检测对认知功能障碍测试比WAIS-RC更敏感,且不受患者的病程、受教育年限、运动功能障碍程度的影响,能客观反映出PD患者认知功能的损害。     

GABAergic and pallidal terminals in the thalamic reticular nucleus of squirrel monkeys

The ultrastructure of synaptic terminals from the external segment of the globus pallidus and of other synaptic terminals positive for gamma-aminobutyric acid (GABA) was examined in the thalamic reticular nucleus (TRN) of squirrel monkeys. Two GABA-positive terminals types were commonly encountered within the TRN neuropil. The most common type of GABAergic terminals (F terminals) are filled with dispersed pleomorphic synaptic vesicles and clusters of mitochondria. These terminals establish multiple symmetric synapses upon the somata and dendrites of TRN neurons. The external pallidal terminals, labeled with WGA-HRP, arise from thinly myelinated axons and correspond to the medium to large F terminals. A less prevalent population of smaller GABAergic synaptic profiles was also identified. The synaptic profiles in this second group contain considerably fewer pleomorphic synaptic vesicles in small irregular clusters and fewer mitochondria, establish symmetric synapses, are postsynaptic to other axonal terminals, are presynaptic to dendrites and soma, and are unlabeled following pallidal injections of WGA-HRP.