CRCNS: Dynamics and mechanisms of rhythmic activity in basal ganglia

CRCNS:基底节节律活动的动力学和机制

基本信息

项目摘要

DESCRIPTION (provided by applicant): The basal ganglia (BG) are a group of subcortical nuclei receiving extensive projections from cortex and sending extensive projections to thalamus and which are, among other things, involved in neural control of movement. Interest in BG physiology is also motivated by BG-related disorders, especially Parkinson's disease (PD) - a major neurodegenerative disorder characterized by chronic dopamine (DA) deficiency resulting in a set of primarily movement-related symptoms. Although BG plays a significant role in motor control and in motor deficits of PD, the physiological mechanisms responsible for this control and for PD motor deficits remain poorly understood. Recent studies indicate that patterns of oscillatory synchronous activity in BG, although very variable, are strongly relevant to BG physiology and BG disorders, such as PD. The dynamics of these oscillations and their mechanisms are the subjects of this study. Patterns of synchronous oscillatory behavior in spiking units and local field potentials (LFP) will be recorded from BG of human patients and analyzed using a method of synchronous episodes detection. Models, which are adequately constrained by the results of analysis of the variable patterns of synchronous activity recorded from the patients, will be developed. This model will be used as a tool to investigate the mechanisms responsible for the origin of intermittent synchronous behavior and thus identify possible mechanisms in vivo. Bifurcations underlying the occurrence of physiologically realistic dynamics in numerical experiments with the full model and in an analytical approach to a reduced system will be studies. As a result, the mechanisms of the intermittent synchronous activity in BG both in the "biological language" (features of synapses, cells, and connectivity, which give birth to intermittent synchrony) and in "mathematical language" (bifurcations in the system, exhibiting realistic rhythmicity) will be understood. Based on the understanding of the mechanisms, potential methods for modulation and suppression of this rhythmicity (which is believed to be pathological) will be suggested. PUBLIC HEALTH RELEVANCE: The project will enhance understanding of physiology of human brain in Parkinson's disease, a major neurodegenerative disorder. The results of the project may assist in development of new therapies for this disease and related disorders.
描述(由申请人提供):基底神经节(BG)是一组皮质下核,接受皮层的广泛投射并向丘脑发送广泛的投射,除其他外,还参与运动的神经控制。BG相关疾病,特别是帕金森病(PD)——一种以慢性多巴胺(DA)缺乏为特征的主要神经退行性疾病,导致一系列主要的运动相关症状,也激发了人们对BG生理学的兴趣。尽管BG在PD的运动控制和运动缺陷中起着重要作用,但对这种控制和PD运动缺陷的生理机制仍知之甚少。最近的研究表明,虽然BG的振荡同步活动模式非常多变,但与BG生理学和BG疾病(如PD)密切相关。这些振荡的动力学及其机制是本研究的主题。将记录人类患者BG中峰值单元和局部场电位(LFP)的同步振荡行为模式,并使用同步事件检测方法进行分析。将开发模型,这些模型将受到对患者记录的同步活动的可变模式的分析结果的充分约束。该模型将被用作研究间歇性同步行为起源机制的工具,从而确定体内可能的机制。将研究在完整模型的数值实验和在简化系统的分析方法中发生的生理现实动力学的分岔。因此,BG中间歇性同步活动的机制将被理解为“生物语言”(突触、细胞和连接性的特征,它们产生了间歇性同步)和“数学语言”(系统中的分岔,表现出现实的节律性)。基于对其机制的理解,将提出调节和抑制这种节律性(被认为是病理性的)的潜在方法。公共卫生相关性:该项目将加强对帕金森病(一种主要的神经退行性疾病)中人脑生理学的理解。该项目的结果可能有助于开发针对这种疾病和相关疾病的新疗法。

项目成果

期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Neural dynamics in parkinsonian brain: the boundary between synchronized and nonsynchronized dynamics.
帕金森氏脑中的神经动力学:同步和非同步动力学之间的边界。
Failure of delayed feedback deep brain stimulation for intermittent pathological synchronization in Parkinson's disease.
  • DOI:
    10.1371/journal.pone.0058264
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Dovzhenok A;Park C;Worth RM;Rubchinsky LL
  • 通讯作者:
    Rubchinsky LL
Basal ganglia modulation of thalamocortical relay in Parkinson's disease and dystonia.
On the origin of tremor in Parkinson's disease.
  • DOI:
    10.1371/journal.pone.0041598
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Dovzhenok A;Rubchinsky LL
  • 通讯作者:
    Rubchinsky LL
Potential mechanisms for imperfect synchronization in parkinsonian basal ganglia.
  • DOI:
    10.1371/journal.pone.0051530
  • 发表时间:
    2012
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Park C;Rubchinsky LL
  • 通讯作者:
    Rubchinsky LL
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LEONID L RUBCHINSKY其他文献

LEONID L RUBCHINSKY的其他文献

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{{ truncateString('LEONID L RUBCHINSKY', 18)}}的其他基金

CRCNS: Dynamics and mechanisms of rhythmic activity in basal ganglia
CRCNS:基底节节律活动的动力学和机制
  • 批准号:
    7777622
  • 财政年份:
    2009
  • 资助金额:
    $ 23.57万
  • 项目类别:

相似海外基金

A basic study of the motor disturbance in basal ganglia diseases
基底神经节疾病运动障碍的基础研究
  • 批准号:
    13680815
  • 财政年份:
    2001
  • 资助金额:
    $ 23.57万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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