SYNCHRONIZED RHYTHMIC ACTIVITY OF THE PALLIDUM
苍白球的同步节律活动
基本信息
- 批准号:6452797
- 负责人:
- 金额:$ 11.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-05-01 至 2002-04-30
- 项目状态:已结题
- 来源:
- 关键词:Parkinson's disease brain electrical activity calcium binding protein calcium channel calcium indicator digital imaging disease /disorder model dopamine electron microscopy electrostimulus immunocytochemistry laboratory rat lenticular nucleus membrane potentials microelectrodes neural conduction neural transmission neuroanatomy neuropharmacology potassium channel subthalamus synapses tissue /cell culture voltage /patch clamp voltage gated channel
项目摘要
A loss of midbrain dopaminergic cells results in parkinsonism. It has been
hypothesized that parkinsonian rigidity and tremor are associated with
abnormal, wide spread synchronized, rhythmic firing of the pallidum. The
goal of this proposal is to reveal the mechanisms responsible for the
synchronized rhythmic activity of the pallidum. Our basic hypothesis is
that the synchronized rhythmic activity is generated because dopamine (DA)
depletion has altered the intrinsic membrane properties and synaptic
inputs of the pallidum.
We hypothesize that pallidal neurons have intrinsic mechanisms for
membrane oscillation, and that the membrane oscillatory mechanism is
controlled by the DAergic innervation from the midbrain and peptidergic
innervations from the neostriatum (Str). To test these hypothesis,
physiological and pharmacological studies will be performed using a whole
cell recording method in slice preparations. Our study will focus on the
potassium and calcium currents involved in the membrane oscillations and
effects of DNA and striatal peptides on these currents. Calcium imaging
will aid in analyzing the distribution of calcium currents along the
dendrites.
We hypothesize that the wide synchronization of activity seen in the
pallidum of parkinsonian subjects is due to changes in synaptic
transmission. Evaluation of this hypothesis should begin with
physiological and anatomical studies. To reveal the properties of unitary
post-synaptic responses of pallidal neurons to striatal, intra-pallidal,
and subthalamic stimulation, and to reveal the effects of DA and striatal
peptides on the strength and duration of unitary post-synaptic responses,
physiological and pharmacological studies will be performed using a whole
cells recording method in slice preparations. All neurons record in the
slice experiments will be further characterized for parvalbumin
immunoreactivity, somato-dendritic morphology, and at the molecular level
for ion channels, receptors, and calcium binding proteins using single
cell RT-PCR techniques.
To reveal the structural bases for the pallidal synchronizations,
intracellular staining of striatal, pallidal, and subthalamic neurons will
be performed in anesthetized rats, and the axons of stained neurons will
then be analyzed, using computer assisted 3-dimensional reconstruction
systems, at both the light and electron microscopic levels. The light
microscopic analysis will reveal the number and distribution of synaptic
boutons of single axons in the pallidum, and the electron microscopic
analysis will reveal the ultrastructure of the synapses, the synaptic
pattern, and the structure post-synaptic to the synapses.
中脑多巴胺能细胞的损失导致帕金森综合征。已经
假设帕金森氏症的强直和震颤与
苍白球异常的、广泛分布的同步的、有节奏的放电。的
这项建议的目的是揭示负责的机制,
苍白球的同步节律活动。我们的基本假设是
同步的节律活动是由多巴胺(DA)
耗尽改变了固有的膜特性和突触
苍白球的输入。
我们假设苍白球神经元有内在的机制,
膜振荡,膜振荡机制是
由中脑DA能神经支配和肽能神经支配控制
来自新纹状体(Str)的神经支配。为了验证这些假设,
生理和药理学研究将使用一个完整的
切片制备中的细胞记录方法。我们的研究将集中在
参与膜振荡的钾电流和钙电流,
DNA和纹状体肽对这些电流的影响。钙成像
将有助于分析钙电流沿着
树突
我们假设,在大脑中看到的广泛的同步活动,
帕金森病患者的苍白球是由于突触
传输对这一假设的评估应该开始于
生理学和解剖学研究。为了揭示酉的性质,
苍白球神经元对纹状体,苍白球内,
和丘脑底核刺激,并揭示DA和纹状体的影响,
肽对单一突触后反应的强度和持续时间的影响,
生理和药理学研究将使用一个完整的
切片制备中的细胞记录方法。所有的神经元都记录在
切片实验将进一步表征小清蛋白
免疫反应性,体细胞树突状形态,并在分子水平上
对于离子通道、受体和钙结合蛋白,
细胞RT-PCR技术。
为了揭示苍白球同步化的结构基础,
纹状体、苍白球和底丘脑神经元的细胞内染色将
在麻醉大鼠中进行,染色神经元的轴突将
然后利用计算机辅助三维重建技术进行分析
系统,在光和电子显微镜水平。光
显微镜分析将揭示突触的数量和分布
苍白球中单个轴突的终扣,以及电子显微镜
分析将揭示突触的超微结构,
模式,以及突触后的结构。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Hitoshi Kita其他文献
Hitoshi Kita的其他文献
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