The Thalamostriatal System and Cognition

丘脑纹状体系统和认知

• 批准号: 9374566
• 负责人: JOCELYNE H BACHEVALIER
• 金额: $ 8.93万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9374566
• 关键词: Acute; Adult; Affect; Anatomy; Applications Grants; Attention; Autopsy; Basal Ganglia; Basal Ganglia Diseases; Behavior; Behavioral; Bilateral; Cell Nucleus; Cells; Centromedian Thalamic Nucleus; Cerebral cortex; Chronic; Cognition; Cognitive; Complex; Corpus striatum structure; Data; Development; Dose; Event; Foundations; Functional Imaging; Functional disorder; Future; Glutamates; Goals; Habits; Human; Huntington Disease; Immunotoxins; Impaired cognition; Impairment; Infarction; Interneurons; Intoxication; Knowledge; Laboratories; Lead; Lesion; Light; Macaca mulatta; Measures; Monkeys; Motor; Neurodegenerative Disorders; Neurons; Neurotoxins; Parafascicular Nucleus; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Patients; Performance; Pilot Projects; Primates; Process; Reaction Time; Rewards; Rodent; Role; Sensory; Short-Term Memory; Source; Stimulus; Symptoms; System; Testing; Thalamic structure; Visuospatial; base; caudate nucleus; cholinergic; cognitive change; cognitive development; cognitive process; cognitive task; experimental study; flexibility; habit learning; human data; memory recognition; neuron loss; nonhuman primate; novel; putamen; response; selective attention

Abstract Neurodegenerative diseases that involve the basal ganglia commonly lead to cognitive impairments. In this proposal, we hypothesize that the massive projections from the thalamic parafascicular (PF) and centromedian (CM) nuclei to the caudate nucleus and the putamen, respectively, are key pathways that regulate cognitive processing, and that lesion of these thalamostriatal systems produce selective attention-related cognitive impairments in behavioral flexibility, habit learning, and possibly other forms of cognition. The CM and PF provide functionally organized glutamatergic projections that target striatal projection neurons and interneurons (particularly cholinergic interneurons). Functional imaging data from human and monkey studies have shown that CM and PF neurons respond strongly to behaviorally significant sensory events. It was also shown that CM/PF inputs to the striatum regulate responses of striatal tonically active neurons (TANs; likely corresponding to cholinergic interneurons) to salient reward-related stimuli, and that inactivation of Pf disrupts performance in attention tasks. Because the CM/PF complex profoundly degenerates early in the course of Parkinson’s disease (PD) and Huntington’s disease (HD), a detailed knowledge of the role of the CM- and PF-striatal projections will help us to understand the importance of the degeneration of these nuclei in the development of cognitive impairments in PD and HD. In this pilot project, we will evaluate the behavioral consequences of selectively lesioning the CM- or Pf-striatal projections in monkeys, using an immunotoxin lesioning approach. These preliminary studies will set the foundation for the development of a future R01 proposal that will assess the contribution of the primate thalamostriatal system to cognition. A better knowledge of the role of this projection system in normal basal ganglia function is essential to gauge the importance of its degeneration in neurodegenerative diseases.

抽象的 涉及基底神经节的神经退行性疾病通常会导致认知障碍。在这个 提案，我们假设来自丘脑毛对（PF）和Centromedian的大规模预测 （CM）分别对尾状核和壳核的核是调节认知的关键途径 处理，以及这些丘脑纹状体系统的病变产生选择性与注意力相关的认知 行为灵活性，习惯学习以及可能的其他形式认知的障碍。 CM和PF提供 靶向纹状体投影神经元和中间神经元的功能组织的谷氨酸能项目 （特别是胆碱能中间神经元）。来自人类和猴子研究的功能成像数据已显示 CM和PF神经元对行为重要的感觉事件的反应强烈。也表明 CM/PF输入纹状体调节通常活性神经元的反应（TAN；可能相应的 到胆碱能中间神经元）以显着奖励相关的刺激，而PF的灭活都破坏了性能 注意任务。因为CM/PF综合体在帕金森氏病的早期就深刻地退化了 （PD）和亨廷顿氏病（HD），详细了解CM和PF - 纹状体项目的作用将 帮助我们了解这些核变性在认知发展中的重要性 PD和HD损伤。在这个试点项目中，我们将评估有选择的行为后果 使用免疫毒素病变方法，将猴子的CM或PF - 纹状体项目病变。这些 初步研究将为未来R01提案的发展奠定基础，该提案将评估 灵长类动物丘脑系统对认知的贡献。更好地了解该投影的作用 正常基底神经节功能中的系统对于衡量其变性的重要性至关重要 神经退行性疾病。