Developing innovative tools to investigate the anatomy and molecular profile of striatal cholinergic interneurons
开发创新工具来研究纹状体胆碱能中间神经元的解剖结构和分子特征
基本信息
- 批准号:9760258
- 负责人:
- 金额:$ 3.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcetylcholineAddressAlzheimer&aposs DiseaseAnatomyAnimal ModelAntibodiesAntigensAtlasesAxonBehaviorBehavioralBiologyBrain DiseasesBrain regionCellsClinicalColorCommunitiesComplexCorpus striatum structureCuesDataDendritesDetectionDevelopmentDiseaseDystoniaElectrophysiology (science)EquilibriumFire - disastersFunctional disorderGlutamatesGoalsImageIn SituInterneuron functionInterneuronsKnowledgeLabelLearningMapsMembraneMethodsMicroscopyMolecularMolecular ProfilingMorphologyMotorNeuritesNeuronsNeurosciencesParkinson DiseasePatternPhysiciansPlayPopulationProcessPropertyProtocols documentationResolutionRoleSamplingScientistSourceSpecificityStereotypingStructural defectStructureTechnologyTerritorialityTestingThickTissue ExpansionTissuesTrainingVertebral columnbasecell typecholinergicfluorophoreinnovationmolecular markerneuronal cell bodyneuropsychiatric disordernoveltool
项目摘要
Abstract
The striatum is a subcortical brain region critical for action selection, learning, and motor behavior.
Striatal cholinergic interneurons (ChIs) are the primary source of local acetylcholine, and play an
important role in modulating striatal circuits. Consequently, ChIs are dysregulated in many
neuropsychiatric disorders that involve striatal dysfunction, such as Parkinson's disease, Alzheimer's
disease, and dystonia. Despite their importance, little is known about ChI structure and function. ChIs are
a sparse cell type, comprising only ~1% of all striatal neurons, yet have tremendous territorial influence
by sending out dense projections. The complete morphology and local network anatomy of ChIs remain
unknown. Furthermore, a recent study suggested ChIs are not homogenous as previously believed, but
may be divided into subtypes based on morphology and molecular markers. However, the correlation
between ChI anatomy and molecular profiles has yet to be elucidated.
This proposal seeks to expand our understanding of ChI anatomy and molecular profiles by
developing new tools to answer questions that were impossible to address before. Although previously
understood to be an aspiny, homogenous population, my preliminary data demonstrates the existence of
a new ChI morphological subtype: spiny ChIs. I will characterize the complete morphologies of spiny and
aspiny ChIs by combining Brainbow with new clearing and expansion technology. I will then develop
technology to simultaneously visualize morphology and interrogate the molecular profile of ChIs in order
to correlate the two. These studies will increase our understanding of ChI cell types, and reveal
fundamental principles of how their anatomy and molecular profiles contribute to function. The novel tools
developed in this project will also be disseminated for the benefit of the neuroscience community. Finally,
completing this proposal will help drive me towards my long-term goal of becoming a physician scientist
by providing me with rigorous scientific, technical, and clinical training.
抽象的
纹状体是皮质下大脑区域,对于动作选择、学习和运动行为至关重要。
纹状体胆碱能中间神经元(ChIs)是局部乙酰胆碱的主要来源,并发挥着重要作用
在调节纹状体回路中发挥重要作用。因此,ChI 在许多方面都失调
涉及纹状体功能障碍的神经精神疾病,例如帕金森病、阿尔茨海默病
疾病和肌张力障碍。尽管 ChI 很重要,但人们对 ChI 的结构和功能知之甚少。 ChI 是
一种稀疏细胞类型,仅占所有纹状体神经元的 1%,但具有巨大的领域影响力
通过发出密集的投影。 ChI 的完整形态和局部网络解剖仍然存在
未知。此外,最近的一项研究表明 ChI 并不像之前认为的那样同质,而是
可以根据形态和分子标记分为亚型。然而,相关性
ChI 解剖学和分子谱之间的关系尚未阐明。
该提案旨在通过以下方式扩大我们对 ChI 解剖学和分子谱的理解:
开发新工具来回答以前无法解决的问题。虽然之前
被理解为是一个无骨的、同质的群体,我的初步数据表明存在
一种新的 ChI 形态亚型:多刺 ChIs。我将描述刺和刺的完整形态
aspiny ChI 通过将 Brainbow 与新的清算和扩展技术相结合。然后我会发展
技术可同时可视化形态并按顺序询问 ChI 的分子图谱
将两者关联起来。这些研究将增加我们对 ChI 细胞类型的了解,并揭示
它们的解剖结构和分子结构如何发挥功能的基本原理。新颖的工具
该项目中开发的成果也将被传播,以造福神经科学界。最后,
完成此提案将有助于推动我实现成为一名医师科学家的长期目标
为我提供严格的科学、技术和临床培训。
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)
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Fred Yonghe Shen其他文献
Fred Yonghe Shen的其他文献
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{{ truncateString('Fred Yonghe Shen', 18)}}的其他基金
Developing innovative tools to investigate the anatomy and molecular profile of striatal cholinergic interneurons
开发创新工具来研究纹状体胆碱能中间神经元的解剖结构和分子特征
- 批准号:
9911988 - 财政年份:2019
- 资助金额:
$ 3.66万 - 项目类别:
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