Trans-Synaptic Tracing of Developing Somatosensory Circuits

发育中的体感回路的跨突触追踪

• 批准号: 9066828
• 负责人: JANE DODD
• 金额: $ 20万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9066828
• 关键词: Adult; Afferent Neurons; Animals; Attenuated; Cells; Development; Dorsal; Embryo; Environment; Esthesia; Gene Expression Profile; Health; Imagery; Individual; Infection; Knowledge; Label; Mediating; Methodology; Methods; Mus; Nervous system structure; Neurons; Pain; Perception; Perinatal; Phase; Population; Positioning Attribute; Posterior Horn Cells; Property; Rabies virus; Research; Sensory; Skin; Skin Temperature; Specificity; Spinal; Spinal cord injury; Staging; Stimulus; Synapses; System; Techniques; Testing; Touch sensation; Travel; Virus Diseases; cell type; dorsal horn; forging; in utero; mature animal; postnatal; relating to nervous system; somatosensory; therapeutic development

 DESCRIPTION (provided by applicant): Summary A major issue in understanding the development of central somatosensory circuitry is the lack of available markers that permit observation of the paths taken and choices made by individual classes of spinal sensory neurons between initial specification of neural identity, and the establishment of central connections. For this reason it also remains unclear which embryonic subsets of dorsal spinal neuron become those that subserve each distinct somatosensory function. Although many subsets of dorsal horn neuron have been delineated during differentiation and early migratory phases of development, there is a fundamental need to bridge the period when neurons can be identified according to their transcriptional signature and when they can be identified according to their functional circuitry. Methods are required that permit visualization of the synaptic connections between functional classes of DRG neurons and individual classes of dorsal horn neuron and allow us to determine where and how those dorsal horn neurons project centrally during development and in the adult. The recent demonstration that attenuated rabies virus can be directed to specific cell types in the mature nervous system and travel transsynaptically from sensory neurons in the periphery into target central neurons, provides a way to explore the development of the central somatosensory system, defining functional connections through the establishment of synapses, permitting the assignment of function to embryonically identified neurons and conferring a marking technique that allows visualization of the central paths forged y individual classes of dorsal horn neuron. The object of the research in this R21 is to develop methodology that will permit selective anterograde and retrograde transsynaptic tracing of developing somatosensory circuitry during development and to establish the techniques for general use in developing systems.

 描述(由申请人提供)：摘要理解中枢躯体感觉回路发展的一个主要问题是缺乏可用标记来观察不同类别的脊髓感觉神经元在最初指定神经身份和建立中枢连接之间所采取的路径和作出的选择。出于这个原因，还不清楚背侧脊髓神经元的哪些胚胎亚群成为那些辅助每种不同的躯体感觉功能的亚群。尽管背角神经元的许多亚群在发育的分化和早期迁移阶段被描绘出来，但仍然有必要在根据其转录特征识别神经元和根据其功能电路识别神经元的时间段之间架起桥梁。需要一些方法来可视化功能类型的背根节神经元和不同类型的背角神经元之间的突触联系，并允许我们确定这些背角神经元在发育过程中和在成人中集中投射的位置和方式。最近的研究表明，狂犬病减毒病毒可以定向到成熟神经系统中的特定细胞类型，并从周围的感觉神经元跨突触进入靶中枢神经元，这为探索中枢躯体感觉系统的发展提供了一条途径，通过建立突触来定义功能联系，允许将功能分配给胚胎识别的神经元，并提供了一种标记技术，允许可视化由单个类型的背角神经元形成的中心路径。R21的研究目的是开发一种方法学，允许在发育过程中对发育中的体感回路进行选择性的顺行和逆行跨突触追踪，并建立在开发系统中普遍使用的技术。