THE THALAMOSTRIATAL SYSTEM IN PRIMATES

灵长类动物的丘脑纹状体系统

• 批准号: 8357447
• 负责人: Yoland Smith
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357447
• 关键词: Animal Model; Animals; Autopsy; Brain; Brain region; Corpus striatum structure; Data; Dendritic Spines; Electrons; Funding; Glutamate Transporter; Glutamates; Grant; Human; Light; Microscopic; Monkeys; Morphology; National Center for Research Resources; Parkinson Disease; Parkinsonian Disorders; Patients; Pattern; Physiological; Presynaptic Terminals; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Rodent Model; Source; Synapses; System; Thalamic structure; United States National Institutes of Health; Vertebral column; cost; density

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is compelling evidence from animal models and postmortem human brains of Parkinson's disease (PD) patients that striatal spine loss is a key neuropathological feature of PD. Knowing that striatal glutamatergic afferents target dendritic spines, these data appear difficult to reconcile with physiological studies showing overactivity of the corticostriatal glutamatergic system in rodent models of parkinsonism, and evidence for an increased expression of the vesicular glutamate transporter type I (vGluT1), a marker of cortical terminals, in the striatum of PD patients and MPTP-treated monkeys. In light of data from other brain regions suggesting a tight correlation between morphology and function of axo-spinous glutamatergic synapses, we undertook a detailed ultrastructural analysis of corticostriatal (vGluT1-positive) and thalamostriatal (vGluT2-positive) axo-spinous glutamatergic synapses using a 3D electron microscopic approach in normal and MPTP-treated monkeys. Three main conclusions can be drawn from this analysis: (1) The spines contacted by cortical vGluT1-containing terminals have a larger volume and harbor significantly larger post-synaptic densities (PSDs) than those contacted by vGluT2-immunoreactive thalamic boutons, (2) A subset of thalamic, but not cortical, terminals display a pattern of multisynaptic connectivity in normal and MPTP-treated monkeys and (3) Both cortical and thalamic axo-spinous synapses undergo ultrastructural changes (larger spine volume, larger PSDs, larger pre-synaptic terminal) indicative of increased synaptic activity in parkinsonian animals.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 来自帕金森病 (PD) 患者的动物模型和死后人类大脑提供了令人信服的证据，表明纹状体棘缺失是 PD 的一个关键神经病理学特征。知道纹状体谷氨酸传入神经以树突棘为目标，这些数据似乎很难与生理学研究相一致，这些研究表明帕金森病啮齿动物模型中皮质纹状体谷氨酸系统过度活跃，并且有证据表明 I 型囊泡谷氨酸转运蛋白 (vGluT1) 表达增加，这是一种标志物PD 患者和 MPTP 治疗猴子的纹状体中的皮质末梢。根据来自其他大脑区域的数据表明轴棘谷氨酸突触的形态和功能之间存在紧密相关性，我们使用正常猴子和 MPTP 治疗猴子的 3D 电子显微镜方法。从该分析中可以得出三个主要结论：（1）与 vGluT2 免疫反应性丘脑纽扣相比，包含 vGluT1 的皮质末端接触的棘具有更大的体积，并且具有显着更大的突触后密度（PSD），（2）在正常和 MPTP 治疗的猴子中，丘脑（但不是皮质）末端的一个子集显示出多突触连接模式，并且 (3) 两者皮质和丘脑轴棘突触经历超微结构变化（更大的脊柱体积、更大的 PSD、更大的突触前末端），表明帕金森病动物的突触活动增加。