The Thalamostriatal System and Cognition

丘脑纹状体系统和认知

基本信息

  • 批准号:
    9374566
  • 负责人:
  • 金额:
    $ 8.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 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

项目摘要

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.
摘要 涉及基底神经节的神经退行性疾病通常导致认知障碍。在这 建议,我们假设,从丘脑旁束(PF)和中央正中的大量投射 (CM)核到尾状核和壳核,分别是调节认知的关键途径, 这些丘脑-纹状体系统的损伤会产生选择性注意相关的认知功能障碍。 行为灵活性、习惯学习和可能的其他形式的认知的损伤。CM和PF提供 以纹状体投射神经元和中间神经元为目标的功能性组织的纹状体能投射 (尤其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显示, CM和PF神经元对行为上重要的感觉事件反应强烈。还显示 纹状体的CM/PF输入调节纹状体紧张性活性神经元(TAN;可能对应于 对胆碱能中间神经元)对显着奖励相关刺激的反应,并且Pf的失活会扰乱表现 注意力任务。因为CM/PF复合体在帕金森病的早期就严重退化 (PD)和亨廷顿病(HD),详细了解CM和PF纹状体投射的作用将 帮助我们理解这些核团的退化在认知发展中的重要性, PD和HD的损伤。在这个试点项目中,我们将评估选择性地 使用免疫毒素损伤方法损伤猴子的CM-或PF-纹状体投射。这些 初步研究将为未来R 01提案的制定奠定基础,该提案将评估 灵长类丘脑纹状体系统对认知的贡献。更好地了解这一预测的作用 正常基底神经节功能的系统是必不可少的,以衡量其退化的重要性, 神经退行性疾病

项目成果

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JOCELYNE H BACHEVALIER其他文献

JOCELYNE H BACHEVALIER的其他文献

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{{ truncateString('JOCELYNE H BACHEVALIER', 18)}}的其他基金

Cycles of Social Contingency: Pivotal Transitions that Shape Brain-Behavior Development in Monkeys
社会偶然事件的循环:塑造猴子大脑行为发展的关键转变
  • 批准号:
    10227975
  • 财政年份:
    2012
  • 资助金额:
    $ 8.93万
  • 项目类别:
Cycles of Social Contingency: Pivotal Transitions that Shape Brain-Behavior Development in Monkeys
社会偶然事件的循环:塑造猴子大脑行为发展的关键转变
  • 批准号:
    10005485
  • 财政年份:
    2012
  • 资助金额:
    $ 8.93万
  • 项目类别:
PRIMATE AMYGDALA AND THE CONTROL OF VISUAL SEARCH OF EMOTIONAL STIMULI
灵长类杏仁核和情绪刺激视觉搜索的控制
  • 批准号:
    8357536
  • 财政年份:
    2011
  • 资助金额:
    $ 8.93万
  • 项目类别:
SAFETY SIGNAL LEARNING IN MONKEYS: CORTICAL REGULATION AND ITS DEVELOPMENT
猴子的安全信号学习:皮质调节及其发展
  • 批准号:
    8357501
  • 财政年份:
    2011
  • 资助金额:
    $ 8.93万
  • 项目类别:
CONTINUITY OF THE LIMBIC CIRCUIT THROUGH THE BASAL GANGLIA
边缘回路通过基底神经节的连续性
  • 批准号:
    8357500
  • 财政年份:
    2011
  • 资助金额:
    $ 8.93万
  • 项目类别:
DEVELOPMENT OF MEDIAL TEMPORAL LOBE FUNCTIONS
内侧颞叶功能的发育
  • 批准号:
    8357420
  • 财政年份:
    2011
  • 资助金额:
    $ 8.93万
  • 项目类别:
CONTINUITY OF THE LIMBIC CIRCUIT THROUGH THE BASAL GANGLIA
边缘回路通过基底神经节的连续性
  • 批准号:
    8172463
  • 财政年份:
    2010
  • 资助金额:
    $ 8.93万
  • 项目类别:
DEVELOPMENT OF MEDIAL TEMPORAL LOBE FUNCTIONS
内侧颞叶功能的发育
  • 批准号:
    8172352
  • 财政年份:
    2010
  • 资助金额:
    $ 8.93万
  • 项目类别:
SAFETY SIGNAL LEARNING IN MONKEYS: CORTICAL REGULATION AND ITS DEVELOPMENT
猴子的安全信号学习:皮质调节及其发展
  • 批准号:
    8172464
  • 财政年份:
    2010
  • 资助金额:
    $ 8.93万
  • 项目类别:
NEURAL SUBSTRATES CROSS-MODAL INTEGRATION OF SOCIO-EMOTIONAL CUES: PET IMAGING
社会情感线索的跨模式整合的神经基质:PET 成像
  • 批准号:
    7958225
  • 财政年份:
    2009
  • 资助金额:
    $ 8.93万
  • 项目类别:

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