Actin-based Neuronal State Changes
基于肌动蛋白的神经元状态变化
基本信息
- 批准号:7488953
- 负责人:
- 金额:$ 38.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-08-25 至 2011-07-31
- 项目状态:已结题
- 来源:
- 关键词:ActinsAgingAnimalsBehaviorBiochemistryBiologicalBrainCell divisionCell physiologyCellsChromosome PairingCognitionCultured CellsCytoskeletonDevelopmentDrug AddictionFunctional disorderGenesGenetic TranscriptionGlutamatesGoalsImageIntracellular TransportLearningLocalizedMediatingMemory impairmentMethodsModificationMolecularMovementNatureNerve DegenerationNeurobiologyNeuronsProcessPublic HealthRattusRoleSignal TransductionSiteSleep DisordersSliceStimulusSynapsesSystemTestingTranscriptional Activationactin 2basebehavior changebehavior measurementbeneficiarycell transformationdisorder preventionexperienceextracellularinsightmouse modelnervous system disorderneuronal cell bodyneurotransmissionrelating to nervous systemsuprachiasmatic nucleus
项目摘要
DESCRIPTION (provided by applicant): Dynamic assembly and disassembly of the actin cytoskeleton underlies diverse cellular processes, including cell division, developmental polarity and intracellular transport. These changes can be local or global, transforming cell state. Extracellular signals mediate experience-induced changes of actin dynamics within synaptic microdomains of neurons. Recent evidence suggests that actin dynamics of the cell body, distinct from those in the synapse, also may be necessary for neurons to sense and respond to extracellular stimuli. We predict that this process contributes to plasticity of behavior by altering transcription. Our overarching goal is to understand how experience signals long-term state changes in neurons that, in turn, change behavior. We hypothesize that glutamatergic neurotransmission changes actin organization, and this is permissive for transcriptional activation. We will test this hypothesis in the suprachiasmatic nucleus (SCN), a brain site with established molecular substrates necessary for temporal organization of behavior. The SCN is a cell-based, ~24-h clock driven by spatial and temporal oscillations that regulate transcription. Specifically, we hypothesize that signaling cascades initiated by glutamate engage the actin cytoskeleton of SCN cells, changing localization of key transcriptional regulators that alter clock state. We will examine the nature and necessity of such changes in actin and their effects on transcriptional activation of clock genes. We will evaluate these mechanisms in rat and mouse models: cell cultures, brain slices and behaving animals. Specific aims will: 1) characterize and localize stimulus-induced changes in actin; 2) find the role of actin changes in clock function and behavior, and 3) determine the role of actin changes in regulating transcription. We will use cell biological methods, dynamic imaging, biochemistry, neurobiological measures, and behavioral analyses. The breadth of this systems-based analysis will generate insights into how experience is transformed into long-lasting modification in brain state and behavior. This will enhance the understanding of substrates of long-lasting neural state change, with broad relevance for public health and disease prevention. Dysfunctions in the actin system cause severe neurological disorders, including those of cognition, neurodegeneration, movement and autonomic control. Sleep disorders, learning/memory impairments, drug-addiction and aging will be direct beneficiaries.
描述(由申请人提供):肌动蛋白细胞骨架的动态组装和拆卸是多种细胞过程,包括细胞分裂,发育极性和细胞内转运。这些变化可以是局部或全局,改变细胞状态。细胞外信号介导了经验诱导的神经元突触微区内肌动蛋白动力学的变化。最近的证据表明,与突触中的肌动蛋白动力学不同,神经元也可能需要对细胞外刺激进行感觉和反应。我们预测,此过程通过改变转录来有助于行为的可塑性。我们的总体目标是了解经验如何表示神经元中的长期状态变化,而神经元又改变行为。我们假设谷氨酸能神经传递会改变肌动蛋白组织,这是转录激活的允许性。我们将在脑部核(SCN)中检验该假设,这是一个大脑部位,具有既定的分子底物是行为时间的必要的分子底物。 SCN是一个基于细胞的〜24小时时钟,由调节转录的空间和时间振荡驱动。具体而言,我们假设谷氨酸引发的信号级联反应与SCN细胞的肌动蛋白细胞骨架相关,从而改变了改变时钟状态的关键转录调节剂的定位。我们将研究肌动蛋白发生这种变化及其对时钟基因转录激活的影响的性质和必要性。我们将在大鼠和小鼠模型中评估这些机制:细胞培养物,脑切片和行为动物。具体目的将:1)表征和定位刺激引起的肌动蛋白变化; 2)找到肌动蛋白在时钟功能和行为中的作用,3)确定肌动蛋白变化在调节转录中的作用。我们将使用细胞生物学方法,动态成像,生物化学,神经生物学测量和行为分析。这种基于系统的分析的广度将对经验如何转化为大脑状态和行为的长期修饰。这将增强对持续神经状态变化的基板的理解,并与预防公共卫生和疾病相关。肌动蛋白系统中的功能障碍会引起严重的神经系统疾病,包括认知,神经退行性,运动和自主控制。睡眠障碍,学习/记忆力障碍,吸毒和衰老将是直接受益人。
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 }}
Martha U Gillette其他文献
Martha U Gillette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('Martha U Gillette', 18)}}的其他基金
Dynamic Circadian Regulation of the Blood-Brain Interface in a Human Brain-mimicking Microfluid Chip
模拟人脑微流体芯片中血脑界面的动态昼夜节律调节
- 批准号:
10318466 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
Dynamic Circadian Regulation of the Blood-Brain Interface in a Human Brain-mimicking Microfluid Chip
模拟人脑微流体芯片中血脑界面的动态昼夜节律调节
- 批准号:
10912839 - 财政年份:2021
- 资助金额:
$ 38.75万 - 项目类别:
High Resolution Analysis of miR125b in Dendrites via Microfluidic Devices
通过微流体装置对树突中的 miR125b 进行高分辨率分析
- 批准号:
8571230 - 财政年份:2013
- 资助金额:
$ 38.75万 - 项目类别:
相似国自然基金
纳米稀土CeO2在土壤-动物体系中的形态转化、累积分布及毒性作用机制
- 批准号:41877500
- 批准年份:2018
- 资助金额:62.0 万元
- 项目类别:面上项目
miR-34c在保护高糖诱导的VSMCs早衰并延缓糖尿病血管老化与钙化中的作用及机制
- 批准号:81770833
- 批准年份:2017
- 资助金额:56.0 万元
- 项目类别:面上项目
缝隙连接蛋白26在老年性耳聋中的表达及其甲基化作用机制研究
- 批准号:81500795
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
研究细胞/组织器官衰老与机体衰老关联机制的条件性敲入小鼠模型的建立与分析
- 批准号:81571374
- 批准年份:2015
- 资助金额:120.0 万元
- 项目类别:面上项目
改善年龄老化导致下肢新生血管生成障碍的实验研究
- 批准号:81070257
- 批准年份:2010
- 资助金额:30.0 万元
- 项目类别:面上项目
相似海外基金
Genetic Analyses of Dendrite Morphogenesis in Caenorhabditis Elegans
秀丽隐杆线虫树突形态发生的遗传分析
- 批准号:
10736702 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Fertilization-induced maturation of cortical ER clusters in oocytes; impact of maternal age
受精诱导卵母细胞皮质 ER 簇的成熟;
- 批准号:
10720185 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Probing how hair bundle mechanical properties shape the mechanotransducer receptor current
探讨发束机械特性如何塑造机械传感器受体电流
- 批准号:
10778103 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Unanticipated roles of C5aR1 Signaling Leading from Acute to Chronic Kidney Disease
C5aR1 信号转导从急性肾病到慢性肾病的意外作用
- 批准号:
10591053 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别:
Molecular and Cell Biological Foundations of Proteostress-Induced Neuronal Extrusion
蛋白质应激诱导的神经元挤压的分子和细胞生物学基础
- 批准号:
10753902 - 财政年份:2023
- 资助金额:
$ 38.75万 - 项目类别: