A Tonically Active Network in the Neostriatum
新纹状体中的紧张活跃网络
基本信息
- 批准号:8458120
- 负责人:
- 金额:$ 27.45万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAction PotentialsAnimalsAxonBasal GangliaBasal Ganglia DiseasesBradykinesiaCellsCholinergic ReceptorsChronicCorpus striatum structureCouplingDataDeep Brain StimulationDependenceDiseaseDopamineElectrical SynapseElectrodesExperimental Animal ModelExperimental ParkinsonismFire - disastersFrequenciesFutureGap JunctionsGenerationsGoalsHumanInterneuronsIon ChannelKnowledgeMeasuresMonkeysMovementNatureNeostriatumNeuronsNitric OxideNoiseOutputOxidopamineParkinson DiseaseParkinsonian DisordersPatternPhasePopulationPropertyReceptor ActivationSignal TransductionSliceSomatostatinSubstantia nigra structureSymptomsSynapsesSynaptic plasticityTestingThalamic structureWorkbasecell typecholinergiccholinergic neurondirected attentiondopaminergic neuronextracellularin vivoneuropeptide Ynext generationpromoterresearch studyresponsespatiotemporalstability testingtherapeutic target
项目摘要
DESCRIPTION (provided by applicant): Recent advances in the study of human Parkinson's disease and experimental animal models of the disease have directed attention to oscillatory electrical activity in the basal ganglia. Low frequency oscillations in the beta range (13-30 Hz) have been shown to be exaggerated in Parkinson's disease, and to occur normally when movements are inhibited. The oscillations are measured as field potentials using gross electrodes, so their cellular origins are not known, but they are in part generated in the striatum. Because field potentials are a population measure, they must reflect synchronous activity in groups of neurons. Studies of experimental parkinsonism in monkeys have shown that neurons firing in rhythm with the low frequency oscillation are all tonically active striatal interneurons. These cells maintain their background firing, even when animals are not moving. In contrast, the principal cells of the striatum, the spiny neurons, and the best-studied interneurons (the fast-spiking interneurons) fire episodically in relation to movement and are mostly silent otherwise. Thus, the striatal generator for the low frequency oscillations associated with bradykinesia is probably tonically firing interneurons. It has previously been thought that all tonically active interneurons in the striatum are cholinergic interneurons. Recently, it has become clear that there are two kinds of tonically active interneurons in the striatum (i.e. active in the absence of excitation from elsewhere). They are the cholinergic interneuron and the LTS (low-threshold spike) bursting interneuron. Together, these two neuron types comprise a spontaneously active network in the striatum that generates continuous oscillatory activity, even in the absence of input. The spontaneously active network receives sparser synaptic input from striatal afferents, and interacts with the phasic striatal cells primarily by way of neuromodulatory control of excitability and synaptic plasticity via acetylcholine, nitric oxide, somatostatin, and neuropeptide Y. The experiments proposed here will determine the connectivity and dynamic properties of the network of spontaneously-active interneurons. They will determine whether the intrinsic resonant properties of the network consisting of tonically active striatal interneurons are appropriate for generation of oscillations in the beta frequency band. We will determine the mechanism of spontaneous oscillations in LTS cells, and whether synaptic connections between them act to promote or oppose synchronous activity. We will also examine the changes in the intrinsic oscillations and synchronization that follow chronic dopamine depletion with 6- hydroxydopamine. The two autonomously active cell types can be readily identified in slices, and targeted for study. These experiments will reveal mechanisms promoting synchronization that may be points of action of dopaminergic depletion and possible targets for future anti-parkinsonian therapies.
描述(申请人提供):人类帕金森氏病研究的最新进展和该疾病的实验动物模型已将注意力集中在基底节的振荡电活动上。在贝塔范围(13-30赫兹)的低频振荡已被证明在帕金森氏症中被夸大,当运动被抑制时正常发生。这种振荡是用粗大的电极作为场电位来测量的,因此它们的细胞起源尚不清楚,但它们部分是在纹状体产生的。因为场电位是一种群体测量,所以它们必须反映神经元群中的同步活动。对猴子实验性帕金森综合征的研究表明,与低频振荡有节奏地放电的神经元都是紧张性活跃的纹状体中间神经元。即使在动物不动的时候,这些细胞也会保持它们的背景放电。相比之下,纹状体的主细胞、棘神经元和研究最深入的中间神经元(快速尖峰中间神经元)与运动有关时会时断时续地发出信号,否则大多是沉默的。因此,与运动迟缓相关的低频振荡的纹状体生成器可能正在调谐地激发中间神经元。以往的研究认为,纹状体中所有强直活动的中间神经元都是胆碱能中间神经元。最近发现,纹状体中有两种调频活动的中间神经元(即在没有其他刺激的情况下活动)。它们是胆碱能中间神经元和低阈值放电中间神经元。这两种类型的神经元共同构成了纹状体中的自发活动网络,即使在没有输入的情况下,该网络也会产生持续的振荡活动。自发活动网络从纹状体传入接受较稀疏的突触输入,主要通过乙酰胆碱、一氧化氮、生长抑素和神经肽Y对兴奋性和突触可塑性进行神经调节控制而与时相纹状体细胞相互作用。本实验将确定自发活动中间神经元网络的连通性和动力学特性。他们将确定由音调活跃的纹状体中间神经元组成的网络的固有共振特性是否适合在β频段产生振荡。我们将确定LTS细胞自发振荡的机制,以及它们之间的突触连接是促进还是反对同步活动。我们还将研究6-羟基多巴胺慢性耗竭后固有振荡和同步性的变化。这两种自主活跃的细胞类型可以很容易地在切片上识别出来,并成为研究的目标。这些实验将揭示促进同步化的机制,这些机制可能是多巴胺能耗竭的作用点,也可能是未来抗帕金森病治疗的靶点。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Charles J Wilson其他文献
Random behavior in regular spike times: a phase function to find periodicity in spike time sequences, and its application to globus pallidus neurons
- DOI:
10.1186/1471-2202-11-s1-p8 - 发表时间:
2010-07-20 - 期刊:
- 影响因子:2.300
- 作者:
Ramana Dodla;Charles J Wilson - 通讯作者:
Charles J Wilson
Chaotic decorrelation of Globus Pallidus by periodic forcing: a possible mechanism for the therapeutic effects of deep brain stimulation
- DOI:
10.1186/1471-2202-12-s1-f3 - 发表时间:
2011-07-18 - 期刊:
- 影响因子:2.300
- 作者:
Charles J Wilson;Bryce Beverlin;Theoden Netoff - 通讯作者:
Theoden Netoff
Noise-induced speed up in repetitively firing neurons occurs far from spike threshold
- DOI:
10.1186/1471-2202-15-s1-p11 - 发表时间:
2014-07-21 - 期刊:
- 影响因子:2.300
- 作者:
Todd W Troyer;David Barraza;Michael A Farries;Charles J Wilson - 通讯作者:
Charles J Wilson
Phase response curves of subthalamic neurons: experimental measurement and theoretical prediction
- DOI:
10.1186/1471-2202-12-s1-p370 - 发表时间:
2011-07-18 - 期刊:
- 影响因子:2.300
- 作者:
Michael A Farries;Charles J Wilson - 通讯作者:
Charles J Wilson
Activity-independent intracellular signaling contributes to rate variability among neurons in the globus pallidus.
- DOI:
10.1186/1471-2202-11-s1-p152 - 发表时间:
2010-07-20 - 期刊:
- 影响因子:2.300
- 作者:
Christopher A Deister;Ramana Dodla;David Barraza;Charles J Wilson - 通讯作者:
Charles J Wilson
Charles J Wilson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Charles J Wilson', 18)}}的其他基金
Oscillations and Resonance in Basal Ganglia Circuits
基底神经节回路中的振荡和共振
- 批准号:
10530701 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Oscillations and Resonance in Basal Ganglia Circuits
基底神经节回路中的振荡和共振
- 批准号:
9146576 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Oscillations and Resonance in Basal Ganglia Circuits
基底神经节回路中的振荡和共振
- 批准号:
10350562 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Oscillations and Resonance in Basal Ganglia Circuits
基底神经节回路中的振荡和共振
- 批准号:
10063570 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Quantitative Neurobiology at the University of Texas at San Antonio
德克萨斯大学圣安东尼奥分校定量神经生物学
- 批准号:
8332587 - 财政年份:2008
- 资助金额:
$ 27.45万 - 项目类别:
相似海外基金
Kilohertz volumetric imaging of neuronal action potentials in awake behaving mice
清醒行为小鼠神经元动作电位的千赫兹体积成像
- 批准号:
10515267 - 财政年份:2022
- 资助金额:
$ 27.45万 - 项目类别:
Signal processing in horizontal cells of the mammalian retina – coding of visual information by calcium and sodium action potentials
哺乳动物视网膜水平细胞的信号处理 â 通过钙和钠动作电位编码视觉信息
- 批准号:
422915148 - 财政年份:2019
- 资助金额:
$ 27.45万 - 项目类别:
Research Grants
CAREER: Resolving action potentials and high-density neural signals from the surface of the brain
职业:解析来自大脑表面的动作电位和高密度神经信号
- 批准号:
1752274 - 财政年份:2018
- 资助金额:
$ 27.45万 - 项目类别:
Continuing Grant
Development of Nanosheet-Based Wireless Probes for Multi-Simultaneous Monitoring of Action Potentials and Neurotransmitters
开发基于纳米片的无线探针,用于同时监测动作电位和神经递质
- 批准号:
18H03539 - 财政年份:2018
- 资助金额:
$ 27.45万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Population Imaging of Action Potentials by Novel Two-Photon Microscopes and Genetically Encoded Voltage Indicators
通过新型双光子显微镜和基因编码电压指示器对动作电位进行群体成像
- 批准号:
9588470 - 财政年份:2018
- 资助金额:
$ 27.45万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10009724 - 财政年份:2018
- 资助金额:
$ 27.45万 - 项目类别:
Enhanced quantitative imaging of compound action potentials in multi-fascicular peripheral nerve with fast neural Electrical Impedance Tomography enabled by 3D multi-plane softening bioelectronics
通过 3D 多平面软化生物电子学实现快速神经电阻抗断层扫描,增强多束周围神经复合动作电位的定量成像
- 批准号:
10467225 - 财政年份:2018
- 资助金额:
$ 27.45万 - 项目类别:
Fast high-resolution deep photoacoustic tomography of action potentials in brains
大脑动作电位的快速高分辨率深度光声断层扫描
- 批准号:
9423398 - 财政年份:2017
- 资助金额:
$ 27.45万 - 项目类别:
NeuroGrid: a scalable system for large-scale recording of action potentials from the brain surface
NeuroGrid:用于大规模记录大脑表面动作电位的可扩展系统
- 批准号:
9357409 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Noval regulatory mechanisms of axonal action potentials
轴突动作电位的新调节机制
- 批准号:
16K07006 - 财政年份:2016
- 资助金额:
$ 27.45万 - 项目类别:
Grant-in-Aid for Scientific Research (C)