Synaptic Transmissions in the Basal Ganglia

基底神经节的突触传递

• 批准号: 8867292
• 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/8867292
• 关键词: Affect; Age-Years; Animal Model; Animals; Area; Basal Ganglia; Behavior; Behavioral; Cell Nucleus; Characteristics; Chemicals; Data; Deep Brain Stimulation; Development; Dopamine; Drug Formulations; Electrocorticogram; Experimental Designs; Feedback; Fire - disasters; Foundations; Frequencies; Future; Generations; Globus Pallidus; Goals; Grant; Health; Human; Individual; Intervention; Investigation; 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; Therapeutic; Viral; Work; aging population; base; 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）：帕金森氏病（PD）是第二个最常见的毁灭性神经退行性疾病，影响65岁以上的个体中高达25％。 PD患者和动物模型的数据表明，帕金森氏症的发展与基底神经节异常强，广泛同步的振荡活性（OS）有关，该振荡活性（OS）在含有中脑多巴胺的神经元变性后发展起来。根据最近的研究，我们假设PD患者多巴胺消耗的基底神经节中异常OS严重取决于一个被称为Globus Pallidus（GPE）外部段（GPE）的核中异常OS的发育，这与基础神经神的大多数核具有较强的神经元联系。该项目的主要目标是揭示GPE的功能和解剖连通性的改变，该连通性是异常OS产生的基础的。具体而言，这笔赠款的目的是揭示多巴胺的耗竭如何改变1）GPE神经元的发射行为，2）在皮质 - 歧义途径中异常OS的电导率，以及3）3）均可延长策略的策略，以使所有策略延伸到所有策略中，以延长了整个策略，以设计出来，并缩小了整个策略。 PD主题。拟议研究的结果将提高我们对病理条件下基底神经节的功能组织的理解，并为未来的研究提供明确的方向，包括制定人类帕金森氏症的治疗策略。