Avian vocal experience and adult neuron replacement.

鸟类发声体验和成人神经元替代。

• 批准号: 7318345
• 负责人: JOHN R KIRN
• 金额: $ 26.19万
• 依托单位: WESLEYAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-26 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7318345
• 关键词: Acute; Address; Adult; Affect; Age; Alkaline Phosphatase; Behavior; Birds; Blood; Brain; Brain region; Cataloging; Catalogs; Causations; Cell Nucleus; Cells; Cellular Morphology; Chronic; Class; Destinations; Deterioration; Development; Efferent Pathways; Foundations; Funding; Future; Genes; Goals; Green Fluorescent Proteins; Human; Label; Learning; Life; Location; Longevity; Maps; Measurement; Measures; Methods; Morphology; Motor; Motor Neurons; Neurons; Population; Production; Property; Range; Rate; Recording of previous events; Reliance; Retroviral Vector; Retroviridae; Sensory; Site; Slice; Songbirds; Source; Staging; Stem cells; Structure; Synapses; Telencephalon; Testing; Time; Tissues; Ventricular; Vertebrates; Work; age effect; auditory feedback; cell type; design; electrical property; experience; neurogenesis; programs; repaired; research study; response; stereotypy; vocal control; vocal learning; vocalization; zebra finch

DESCRIPTION (provided by applicant): Neurogenesis persists into adulthood in many vertebrates including humans. An understanding of the factors that control adult neuron addition, differentiation and survival may ultimately suggest mechanisms for brain repair. In adult warm-blooded vertebrates, the most widespread neuron production occurs in the avian telencephalon. In songbirds, many new projection neurons are inserted into the High Vocal Center (HVC) to become part of the pre-motor, efferent pathway necessary for the production of learned vocalizations. Thus, studies of the avian brain may address basic questions about the mechanisms permitting widespread neuron addition and, at the same time provide an exceptional opportunity to relate neuron addition in discrete brain regions to a well-characterized behavior-song. Deafening leads to song deterioration and the impact on song decreases with increasing bird age or vocal practice. Correlations between singing history, song stereotypy, motor program stability (defined by reliance of song structure on auditory feedback) and neuronal incorporation established during the prior period of support will be directly tested by manipulation of singing prior to deafening. To further explore the functional significance of adult neuronal replacement, selective manipulation of HVC stem cells will be required. Using retroviral methods, the relationship between birthplace and final destination for HVC cells and neurons destined elsewhere in the telencephalon will be mapped. This work will identify sites of HVC stem cells for future manipulation and provide a fate map of the topographical relationship between proliferative zones and the telencephalon more generally. The first comprehensive analysis of adult-formed vocal control neuron structure and electrophysiological properties will also be conducted using retroviral vectors. Morphological comparisons among adult-formed HVC neurons and new neurons dispersed throughout the telencephalon will provide a first appraisal of the adult avian brain's natural potential to produce and integrate multiple neuron classes. Functional properties of adult-formed HVC pre-motor neurons (visualized by retroviral labeling with green fluorescent protein) and sources of synaptic input will be identified by electrophysiological stimulation-recording work in tissue slices as a step toward understanding how these cells are integrated into the brain. Collectively, this work will test the relationship between cell replacement and song, provide basic information about the avian brain's natural potential for producing diverse cell types, and set the stage for future work aimed at testing the functional consequences of suppressing replacement on learned vocal behavior.

描述（由申请人提供）：在包括人类在内的许多脊椎动物中，神经发生持续存在。了解控制成人神经元，分化和存活的因素最终可能提出了脑修复的机制。在成年暖血脊椎动物中，最广泛的神经元产生发生在禽尾脑中。在鸣禽中，许多新的投影神经元被插入高声乐中心（HVC），成为生产学习发声所必需的前运动途径的一部分。因此，对鸟类大脑的研究可能会解决有关允许添加广泛神经元的机制的基本问题，同时为将离散大脑区域中的神经元添加与特征良好的行为为歌曲提供了极大的机会。震耳欲聋会导致歌曲恶化，并且随着鸟类的年龄或人声实践的增加，对歌曲的影响减少。歌唱历史，歌曲定型观念，运动程序稳定性（由听觉反馈中的歌曲结构的依赖定义）与在先前支持期间建立的神经元融合之间的相关性将通过在震耳欲聋之前操纵唱歌直接测试。为了进一步探索成人神经元替代的功能意义，将需要选择性操纵HVC干细胞。使用逆转录病毒方法，将映射出发源地细胞和最终目的地之间的关系。这项工作将确定HVC干细胞的位点以进行未来的操作，并提供更普遍的增生区域与端脑之间地形关系的命运图。还将使用逆转录病毒载体对成人形成的声乐神经元结构和电生理特性进行首次综合分析。成人形成的HVC神经元和分散的新神经元之间的形态学比较将首先评估成人禽大脑的自然潜力，以产生和整合多个神经元类别。成人形成的HVC前运动神经元的功能特性（通过用绿色荧光蛋白进行逆转录病毒标记可视化）和突触输入来源将通过在组织切片中的电生理刺激作品来鉴定，以此作为了解这些细胞如何整合到大脑中的步骤。总的来说，这项工作将测试细胞更换和歌曲之间的关系，提供有关禽大脑生产多种细胞类型的自然潜力的基本信息，并为未来的工作奠定了旨在测试抑制替代替代人声行为的功能后果的阶段。