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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 帕金森氏病（PD）患者的动物模型和死后人类大脑中有令人信服的证据表明，纹状体脊柱丧失是PD的关键神经病理学特征。知道纹状体谷氨酸能传入靶向树突状刺时，这些数据似乎很难与生理学研究相结合，显示帕金森氏症啮齿动物模型中皮质的纹状体谷氨酸能体系过度活动性，并且证据表明囊泡谷氨酸转运剂I型I型（VGLUT1）的表达增加了。 MPTP处理的猴子。根据来自其他大脑区域的数据，表明形态学与轴突棘谷氨酸能突触的功能之间存在密切的相关性，我们对皮质纹状体（VGLUT1阳性）的详细超微结构分析进行了详细的超微结构分析，并使用thalamostriatal（vglut2-Postive）（vglut2-Postive）轴突胶状胶质胶化型胶合胶质胶合剂使用3D DD Intron in in MPTP处理的猴子。可以从该分析中得出三个主要结论：（1）含皮质Vglut1末端接触的棘突具有较大的体积，并且与vglut2-免疫反应性thalamic boutons相比，突触后密度（PSD）的斑点明显大得多，但thalamic boutons，（2）thalamial端子，但thalamial端子的端子，但thalamial端子的端子，但正常和MPTP处理的猴子以及（3）皮质和丘脑轴突棘突触都会发生超微结构变化（较大的脊柱体积，较大的PSD，较大的突触前末端），表明帕金森氏动物突触的增加。