The role of intrinsic variability in the synchronization of pallidal neurons

内在变异在苍白球神经元同步中的作用

• 批准号: 7615302
• 负责人: Christopher Allen Deister
• 金额: $ 3万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7615302
• 关键词: AMPA Receptors; Action Potentials; Affect; Animals; Basal Ganglia; Cells; Computer Simulation; Corpus striatum structure; Coupled; Coupling; Data; Disease; Dopamine; Experimental Models; Fire - disasters; Gated Ion Channel; Globus Pallidus; Goals; Health; In Vitro; Injection of therapeutic agent; Ion Channel; Lead; Measures; Mediating; Methods; Modeling; N-Methylaspartate; Neurons; Noise; Parkinson Disease; Patients; Pattern; Pharmacology; Phase; Phase response curves; Play; Positioning Attribute; Preparation; Primates; Property; Role; Shapes; Slice; Solutions; Source; Stimulus; Symptoms; Synapses; Time; Variant; design; in vivo; interest; network models; patch clamp; research study; response; theories; therapeutic target; voltage

DESCRIPTION (provided by applicant): GABAergic neurons of the globus pallidus play a significant role in the symptoms of Parkinson's disease. Specifically these neurons fire action potentials in a synchronized fashion in Parkinson's disease, contributing to global oscillations seen in the basal ganglia. Under normal conditions these neurons have an interesting property in that they generate their own action potentials in a reliable and rhythmic fashion, but there is some irregularity in the firing pattern. Pallidal neurons are synaptically coupled with one another and share some GABAergic input from the striatum; activating a shared input briefly synchronizes the activity of neurons until intrinsic variability makes the neurons fire out of phase from one another. Therefore, the mechanisms that control variability in the autonomous firing pattern could influence how these neurons synchronize to a shared input. Ion channels that generate the firing pattern are in a key position to influence the variability or precision of the autonomous tiring pattern. Thus, the goals of the proposed studies are to identity the ion channels that control the precision of firing in pallidal neurons and to determine if their pharmacological blockade can influence the way pallidal neurons synchronize after a common input. Electrophysiological recordings will be made in an in vitro slice preparation which will allow us to identify ion channels using pharmacology and determine key ion channel properties. This data will be used to construct a computer model of a pallidal neuron that replicates the observed variability in a realistic way. Recordings from pairs of neurons and analysis of a network model will be used to further determine how the availability of ion channels affects synchrony. Neurons in the globus pallidus synchronize their electrical activity in Parkinson's disease, but the mechanisms leading to this are not known. These studies will investigate the role of specific ion channels in creating or limiting synchronization. Understanding these ion channel's role could lead to new therapies for the symptoms of Parkinson's disease by identifying potential therapeutic targets.

描述（由申请人提供）：苍白球的 GABA 能神经元在帕金森病的症状中发挥重要作用。 具体来说，这些神经元在帕金森病中以同步方式激发动作电位，导致基底神经节中出现的整体振荡。在正常情况下，这些神经元有一个有趣的特性，它们以可靠且有节奏的方式产生自己的动作电位，但放电模式存在一些不规则性。苍白球神经元通过突触相互耦合，并共享一些来自纹状体的 GABA 能输入；激活共享输入会短暂同步神经元的活动，直到内在的可变性使神经元彼此异相放电。因此，控制自主放电模式可变性的机制可能会影响这些神经元如何同步到共享输入。生成放电模式的离子通道对于影响自主轮胎模式的可变性或精度起着关键作用。因此，拟议研究的目标是识别控制苍白球神经元放电精度的离子通道，并确定其药理学阻断是否可以影响苍白球神经元在共同输入后同步的方式。 电生理记录将在体外切片制备中进行，这将使我们能够利用药理学来识别离子通道并确定关键的离子通道特性。这些数据将用于构建苍白球神经元的计算机模型，以现实的方式复制观察到的变异性。神经元对的记录和网络模型的分析将用于进一步确定离子通道的可用性如何影响同步性。 在帕金森病中，苍白球中的神经元同步其电活动，但导致这种情况的机制尚不清楚。这些研究将调查特定离子通道在创建或限制同步中的作用。了解这些离子通道的作用可以通过识别潜在的治疗靶点来开发针对帕金森病症状的新疗法。