Glia in Touch Sensation
神经胶质细胞在触觉中的作用
基本信息
- 批准号:8601910
- 负责人:
- 金额:$ 33.13万
- 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:2011-02-01 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAfferent NeuronsAnimalsAntigen-Presenting CellsAreaBehavioral AssayBiological ModelsCaenorhabditis elegansCaringCationsCell physiologyCellsDyesElectrophysiology (science)Epithelial CellsEpitheliumExcretory functionFamilyFluorescenceGeneticGoalsHairHumanHyperalgesiaImageImaging DeviceIndividualInflammationInjuryIon ChannelKnock-outMammalsMeasurementMeasuresMechanicsMediatingMerkel CellsModelingMolecularMolecular GeneticsMovementNerveNerve EndingsNervous system structureNeurogliaNeuronsOutputPacinian CorpusclesPainPhysiologicalPlayPreparationProcessPublishingReceptor ActivationRegulationRoleRuffinis CorpusclesSensorySkinStimulusStretchingSystemTestingTextureTissuesTouch sensationWorkbaseepithelial Na+ channelextracellularfeedingknock-downmechanical allodyniamembernervous system disorderneuronal excitabilitynoveloffspringoverexpressionpatch clamppublic health relevanceresearch studysensory neuropathysignal processingsocialtool
项目摘要
DESCRIPTION (provided by applicant): We depend on the sense of touch for most individual and social activities. Many forms of injuries and inflammation are accompanied by allodynia and mechanical hyperalgesia, conditions in which innocuous touch stimuli now cause severe pain. Despite its fundamental importance, mechanotransduction remains one of the least understood signaling process, both at the cellular and molecular levels. Touch is transduced by specialized mechanosensors embedded in the skin, most of which are composed of nerve endings and associated glial and epithelial cells. The role of these non-neuronal cells in touch sensation is poorly understood. Our goal is to understand touch sensation by dissecting functional interactions between mechanosensory neurons and glia using genetic, molecular and physiological strategies in C. elegans. Specifically, I hypothesize that such interactions employ the ion channel DELM-1, a member of the DEG/ENaC family of cationic channels, expressed in mechanosensory glia. Based on our preliminary results and what is known about the role of DEG/ENaC channels in epithelia, I hypothesize that glial DELM-1 is needed to control the concentration of K+ in the microenvironment between the neuronal ending and glia. Pilot experiments suggest that DELM-1 is inhibited by mechanical forces. Thus, I also hypothesize that the control of extracellular K+ by DELM-1 is highly dynamic and contributes to adaptation of the mechanosensors. The aims of this proposal are: 1) Does the glial DELM-1 channel regulate the activity of mechanosensory neurons? 2) Does DELM-1 elevate [K+] in the microenvironment between glia and touch neurons? 3) Is the glial DELM-1 channel mechanosensitive? Beautiful work in mammalian tissues using skin-nerve preparation and Von-Frey hair has allowed major progress in our understanding of touch sensation. I have now the unprecedented opportunity to capitalize on this previous work to explore a new area in the field. My work is likely to be relevant to our understanding of how associated cells, including glia, control the function of neurons throughout the nervous system.
描述(由申请人提供):我们在大多数个人和社交活动中都依赖于触觉。许多形式的损伤和炎症都伴有异常性疼痛和机械性痛觉过敏,在这种情况下,无害的触摸刺激现在会引起剧烈的疼痛。尽管机械转导具有根本重要性,但无论是在细胞还是分子水平上,它仍然是人们最不了解的信号传导过程之一。触觉是通过嵌入皮肤的专门机械传感器来传导的,其中大部分由神经末梢和相关的神经胶质细胞和上皮细胞组成。人们对这些非神经元细胞在触觉中的作用知之甚少。我们的目标是通过使用线虫的遗传、分子和生理策略剖析机械感觉神经元和神经胶质细胞之间的功能相互作用来了解触觉。具体来说,我假设这种相互作用利用了离子通道 DELM-1,它是阳离子通道 DEG/ENaC 家族的成员,在机械感觉神经胶质细胞中表达。根据我们的初步结果以及对 DEG/ENaC 通道在上皮细胞中的作用的了解,我推测需要神经胶质 DELM-1 来控制神经元末梢和神经胶质细胞之间的微环境中 K+ 的浓度。初步实验表明 DELM-1 会受到机械力的抑制。因此,我还假设 DELM-1 对细胞外 K+ 的控制是高度动态的,有助于机械传感器的适应。该提案的目的是:1)神经胶质DELM-1通道是否调节机械感觉神经元的活动? 2) DELM-1 是否会升高神经胶质细胞和触觉神经元之间微环境中的 [K+]? 3)胶质细胞DELM-1通道是否具有机械敏感性?使用皮肤神经准备和冯弗雷毛发在哺乳动物组织中所做的出色工作使我们对触觉的理解取得了重大进展。我现在拥有前所未有的机会,可以利用之前的工作来探索该领域的新领域。我的工作可能与我们对相关细胞(包括神经胶质细胞)如何控制整个神经系统神经元功能的理解有关。
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)
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Laura Bianchi其他文献
Laura Bianchi的其他文献
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{{ truncateString('Laura Bianchi', 18)}}的其他基金
Glial ion channels in glia/neurons interactions
神经胶质/神经元相互作用中的神经胶质离子通道
- 批准号:
10749239 - 财政年份:2018
- 资助金额:
$ 33.13万 - 项目类别:
Glial ion channels in glia/neurons interactions.
神经胶质/神经元相互作用中的神经胶质离子通道。
- 批准号:
10349558 - 财政年份:2018
- 资助金额:
$ 33.13万 - 项目类别:
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