Synaptic Transmissions in the Basal Ganglia

基底神经节的突触传递

• 批准号: 9064226
• 负责人: Hitoshi Kita
• 金额: $ 32.81万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9064226
• 关键词: Affect; Age-Years; Animal Model; Animals; Area; Basal Ganglia; Behavior; Behavioral; Cell Nucleus; Characteristics; Chemicals; Data; Deep Brain Stimulation; Development; Dopamine; Electrocorticogram; Feedback; Fire - disasters; Formulation; Foundations; Frequencies; Future; Generations; Globus Pallidus; Goals; Grant; Health; Human; Individual; Intervention; Investigation; Investigational Therapies; Lesion; Literature; Mediating; Methodology; Methods; Midbrain structure; Modification; Neurodegenerative Disorders; Neurons; Parkinson Disease; Parkinsonian Disorders; Pathway interactions; Patients; Pattern; Phase; Physiological; Play; Property; Public Health; Rattus; Research; Role; Signal Transduction; Synapses; Synaptic Transmission; Testing; Thinking; Viral; Work; aging population; base; design; optogenetics; research study; response; small hairpin RNA; treatment strategy

DESCRIPTION (provided by applicant): Parkinson's disease (PD) is the second most common devastating neurodegenerative disorder affecting up to 25% of individuals over 65 years of age. Data from patients and animal models of PD have shown that the development of parkinsonisms is associated with the emergence of abnormally strong and widely synchronized oscillatory activity (OS) of the basal ganglia that developed after degeneration of midbrain dopamine containing neurons. Based on recent studies, we hypothesize that abnormal OS in the dopamine-depleted basal ganglia of PD patients is critically dependent on the development of abnormal OS in a nucleus called the external segment of the globus pallidus (GPe), which has strong neuronal connections with most of other nuclei in the basal ganglia. The main goal of this project is to reveal alterations of the functional and anatomical connectivity of GPe that underlie the generation of abnormal OS. Specifically, the aims of this grant are to reveal how dopamine depletion alters 1) the firing behavior of GPe neurons, 2) the conductivity of abnormal OS in the cortico-striato- GPe pathway, and 3) the properties of subthalamo-GPe loop that amplifies abnormal OS, all of which will provide information for designing experimental therapeutic strategies to reduce behavioral deficits in PD subjects. The results of the proposed studies will advance our understanding of the functional organization of the basal ganglia in pathological conditions and provide clear directions for future investigations including the formulation of treatment strategies of human parkinsonisms.

描述（由申请人提供）：帕金森病（PD）是第二种最常见的破坏性神经退行性疾病，影响高达25%的65岁以上的个体。来自PD患者和动物模型的数据表明，帕金森综合征的发生与基底神经节异常强烈和广泛同步的振荡活动（OS）的出现有关，这些振荡活动是在中脑含多巴胺神经元变性后发生的。基于最近的研究，我们假设PD患者多巴胺耗尽基底神经节中的异常OS严重依赖于称为苍白球（GPe）外部段的核中异常OS的发展，该核与基底神经节中的大多数其他核具有强神经元连接。该项目的主要目标是揭示GPe的功能和解剖连接的改变，这些改变是异常OS产生的基础。具体而言，该资助的目的是揭示多巴胺耗竭如何改变1）GPe神经元的放电行为，2）皮质-纹状体- GPe通路中异常OS的传导性，以及3）放大异常OS的底丘脑-GPe回路的特性，所有这些都将为设计实验治疗策略以减少PD受试者的行为缺陷提供信息。拟议的研究结果将推进我们的理解的功能组织的基底神经节在病理条件下，并提供明确的方向，为未来的调查，包括制定人类帕金森氏症的治疗策略。