THALAMOSTRIATAL SYSTEM IN PARKINSONISM

帕金森症的丘脑纹状体系统

• 批准号: 8172461
• 负责人: Thomas N Wichmann
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172461
• 关键词: Anatomy; Animals; Axon; Cells; Complex; Computer Retrieval of Information on Scientific Projects Database; Corpus striatum structure; Data; Deep Brain Stimulation; Electric Stimulation; Funding; Gilles de la Tourette syndrome; Grant; Institution; Interneurons; Intervention; Intralaminar Nuclear Group; Microinjections; Monkeys; Movement; Neurons; Output; Parafascicular Nucleus; Parkinson Disease; Parkinsonian Disorders; Pathologic; Patients; Physiology; Process; Research; Research Personnel; Resources; Shapes; Source; Stimulus; System; Thalamic structure; Training; United States National Institutes of Health; cholinergic; cholinergic neuron; putamen; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. These studies examine the functional interactions and the anatomy of the connections between the intralaminar nuclei of the thalamus (i.e., the centromedian and parafascicular nuclei (CM/PF)) and the striatum in normal and parkinsonian monkeys. CM and PF send a topographically organized projection to the striatum. Movement-related projections from the CM terminate in the putamen which may act to shape striatal output under normal and pathologic conditions. The CM/PF complex is empirically targeted for neurosurgical interventions, such as deep brain stimulation (DBS), in the treatment of patients with Tourette's syndrome and Parkinson's disease. We have found that electrical CM stimulation with short trains of stimuli results in complex sequences of activation and inhibition in striatal cells, which are most easily explained as the result of intrastriatal spread of activity and processing within the striatal circuitry, for instance through local inhibitory axon collaterals and cholinergic interneurons. The ongoing studies (started earlier this year) contrast striatal responses to CM/PF stimulation in normal and parkinsonian monkeys with a combination of electrophysiologic recordings, microinjections, and anatomic studies. In this funding period, we have started to reconstruct the anatomical inputs from CM to specific dendritic domains of cholinergic striatal interneurons (one of the major striatal recipients of CM inputs). In addition, we are studying CM inputs to chemically defined subtypes of striatal output neurons. Finally, we have started electrophysiological recordings in one animal to study the effects of electrical stimulation of the CM on the activity of cholinergic neurons in the striatum. The proposed studies will provide us with information regarding the anatomy and physiology of the thalamostriatal system, and its involvement in parkinsonism, will clarify the effects of electrical stimulation of CM, and will provide data to help clinicians optimize parameters for CM-DBS therapy in parkinsonian patients.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这些研究检查了正常猴和帕金森猴的丘脑层内核（即中心正中核和束旁核（CM/PF））与纹状体之间的功能相互作用和连接解剖结构。 CM 和 PF 向纹状体发送按地形组织的投影。 CM 的运动相关投射终止于壳核，壳核可能在正常和病理条件下塑造纹状体输出。根据经验，CM/PF 复合体是神经外科干预的目标，例如治疗抽动秽语综合征和帕金森病患者的深部脑刺激 (DBS)。 我们发现，短刺激序列的电 CM 刺激会导致纹状体细胞中复杂的激活和抑制序列，这最容易解释为纹状体电路内活动和处理在纹状体内传播的结果，例如通过局部抑制轴突络脉和胆碱能中间神经元。正在进行的研究（今年早些时候开始）结合电生理记录、显微注射和解剖学研究，对比了正常猴和帕金森猴的纹状体对 CM/PF 刺激的反应。在本次资助期间，我们开始重建从 CM 到胆碱能纹状体中间神经元（CM 输入的主要纹状体接收者之一）特定树突域的解剖输入。 此外，我们正在研究化学定义的纹状体输出神经元亚型的 CM 输入。 最后，我们开始对一只动物进行电生理记录，以研究 CM 电刺激对纹状体胆碱能神经元活动的影响。 拟议的研究将为我们提供有关丘脑纹状体系统的解剖学和生理学及其与帕金森病的参与的信息，将阐明 CM 电刺激的效果，并将提供数据以帮助临床医生优化帕金森病 CM-DBS 治疗的参数患者。