Development and regeneration of auditory interneurons

听觉中间神经元的发育和再生

• 批准号: 6806280
• 负责人: HADLEY W HORCH
• 金额: $ 20.72万
• 依托单位: BOWDOIN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6806280
• 关键词: Orthoptera; afferent nerve; auditory nuclei; cell morphology; confocal scanning microscopy; dendritic cells; denervation; developmental neurobiology; innervation; interneurons; nervous system regeneration; neural plasticity; neurogenesis; neuronal guidance

DESCRIPTION (provided by applicant): The development and maintenance of neuronal form depends on an array of molecular and activity-based cues. While developing neurons are highly susceptible to such cues, this flexible responsiveness appears to wane as neuronal systems age. One of the more striking examples of adult plasticity is the denervationinduced dendritic sprouting of auditory interneurons in the cricket. Unilateral removal of the ear induces interneuron dendrites to aberrantly cross the midline and become innervated by auditory afferents from the contralateral ear (Hoy et al., 1985; Schildberger et al., 1986). This reinnervation is remarkably precise, reinstating interneuron-specific threshold and intensity responses. What factors trigger and guide this compensatory regeneration? The combination of confocal microscopy and modern fluorescent tracers or genetic markers will be used to gain a qualitative and quantitative three-dimensional understanding of the compensatory regeneration of auditory interneurons. In addition, the development of auditory interneurons and their innervating afferents will be described. Standard molecular and cellular techniques, including cloning, in situ hybridization, and immunohistochemistry will be used to search for molecular factors whose expression patterns correlate with stages of development. Since neuronal regeneration may rely on cues utilized during development, these experiments will yield information valuable to the examination of neuronal regeneration. Regeneration experiments, informed by development, will examine how alterations in molecular expression patterns might induce or allow dendritic regeneration. It is hoped that an investigation of this invertebrate regeneration phenomenon will advance the fundamental understanding of the development and plasticity of dendrites, and reveal principles governing neuronal regeneration that may be applicable to all neuronal systems, including mammals.

描述（由申请人提供）：神经元形式的开发和维护取决于一系列分子和基于活性的提示。尽管发展神经元非常容易受到此类提示，但这种灵活的反应能力似乎会随着神经元系统的年龄而减弱。成人可塑性的最引人注目的例子之一是板球中听觉中间神经元的树神经诱导的树突状发芽。耳朵的单侧去除会诱导中间树突异常越过中线，并受到对侧耳朵的听觉传入的支配（Hoy等，1985； Schildberger等，1986）。这种重新连接非常精确，可以恢复间含有特定的阈值和强度响应。哪些因素触发并指导这种补偿性再生？ 共聚焦显微镜和现代荧光示踪剂或遗传标记的组合将用于获得对听觉中间神经元补偿性再生的定性和定量的三维理解。此外，还将描述听觉中间神经元及其支配传入的发展。标准分子和细胞技术，包​​括克隆，原位杂交以及免疫组织化学，将用于搜索其表达模式与发育阶段相关的分子因素。由于神经元的再生可能依赖于开发过程中使用的线索，因此这些实验将产生对神经元再生的有价值的信息。通过发育告知的再生实验将检查分子表达模式的变化如何诱导或允许树突再生。 希望对这种无脊椎动物再生现象的调查能够提高对树突的发展和可塑性的基本理解，并揭示有关神经元再生的原则，这些原则可能适用于所有神经元系统，包括哺乳动物。