Avian vocal experience and adult neuron replacement.

鸟类发声体验和成人神经元替换。

• 批准号: 6986123
• 负责人: JOHN R KIRN
• 金额: $ 27.33万
• 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/6986123
• 关键词: animal communication behavior; auditory deprivation; auditory pathways; auditory stimulus; brain mapping; cell age; cell differentiation; cell growth regulation; cell morphology; deafness; ear surgery; electrophysiology; hearing; neural information processing; neurogenesis; neurophysiology; neuropsychology; noise biological effect; psychoacoustics; songbirds; sound perception; telencephalon; verbal behavior; verbal learning; vocalization

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，神经发生持续到成年期。对控制成年神经元添加、分化和存活的因素的理解可能最终提示脑修复的机制。在成年温血脊椎动物中，最广泛的神经元产生发生在鸟类端脑。在鸣禽中，许多新的投射神经元被插入到高音中心（HVC），成为产生学习发声所必需的前运动传出通路的一部分。因此，鸟类大脑的研究可能会解决有关机制允许广泛的神经元添加的基本问题，并在同一时间提供了一个特殊的机会，将神经元添加在离散的大脑区域的一个很好的特征行为歌曲。耳聋导致鸣唱退化，对鸣唱的影响随着鸟龄的增加或发声练习而减少。在之前的支持期间建立的歌唱历史、歌曲刻板性、运动程序稳定性（通过歌曲结构对听觉反馈的依赖来定义）和神经元结合之间的相关性将通过在震耳欲聋之前操纵歌唱来直接测试。为了进一步探索成体神经元替代的功能意义，需要对HVC干细胞进行选择性操作。使用逆转录病毒的方法，HVC细胞和神经元在端脑其他地方的出生地和最终目的地之间的关系将被映射。这项工作将确定HVC干细胞的网站，为未来的操作，并提供一个更普遍的增殖区和端脑之间的地形关系的命运图。成人形成的发声控制神经元结构和电生理特性的第一次全面分析也将使用逆转录病毒载体进行。成人形成的HVC神经元和新的神经元分散在整个端脑的形态学比较将提供第一个评估的成年禽脑的自然潜力，产生和整合多个神经元类。成人形成的HVC前运动神经元的功能特性（可视化逆转录病毒标记的绿色荧光蛋白）和突触输入的来源将被确定的电生理刺激记录工作在组织切片作为一个步骤，了解这些细胞是如何整合到大脑中。总的来说，这项工作将测试细胞替代和歌曲之间的关系，提供有关鸟类大脑产生不同细胞类型的天然潜力的基本信息，并为未来的工作奠定基础，旨在测试抑制替代对学习发声行为的功能后果。