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) 是第二常见的破坏性神经退行性疾病，影响高达 25% 的 65 岁以上个体。来自 PD 患者和动物模型的数据表明，帕金森病的发生与基底神经节异常强烈且广泛同步的振荡活动 (OS) 的出现有关，这种振荡活动是在中脑含有多巴胺的神经元变性后形成的。根据最近的研究，我们假设 PD 患者多巴胺耗尽的基底神经节中的异常 OS 严重依赖于称为苍白球外段 (GPe) 的核中异常 OS 的发展，该核与苍白球外段 (GPe) 具有很强的神经元连接。基底神经节中的大多数其他核。该项目的主要目标是揭示 GPe 功能和解剖连接的改变，这些改变是异常操作系统生成的基础。具体来说，这项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) 下丘脑-GPe 环路的特性，放大异常的 OS，所有这些都将为设计实验治疗策略提供信息，以减少 PD 受试者的行为缺陷。拟议研究的结果将增进我们对病理条件下基底神经节功能组织的理解，并为未来的研究提供明确的方向，包括制定人类帕金森病的治疗策略。