Avian vocal experience and adult neuron replacement.

描述（由申请人提供）：包括人类在内的许多脊椎动物的神经发生持续到成年期。对控制成年神经元增加、分化和存活的因素的理解可能最终为大脑修复提供机制。在成年温血脊椎动物中，最广泛的神经元生产发生在鸟类的端脑。在鸣禽中，许多新的投射神经元被插入高发声中枢（HVC），成为产生习得发声所必需的前运动、传出通路的一部分。因此，对鸟类大脑的研究可以解决有关允许广泛神经元添加的机制的基本问题，同时提供一个特殊的机会，将离散大脑区域的神经元添加与一种具有良好特征的行为-歌唱联系起来。耳聋会导致鸣声退化，随着鸟龄或发声练习的增加，对鸣声的影响会降低。歌唱历史、歌曲刻板印象、运动程序稳定性（由歌曲结构对听觉反馈的依赖来定义）和在先前支持期间建立的神经元整合之间的相关性将通过在耳聋之前操纵歌唱直接测试。为了进一步探索成人神经元替代的功能意义，需要对HVC干细胞进行选择性操作。利用逆转录病毒方法，将绘制出HVC细胞的出生地和最终目的地之间的关系，以及端脑其他地方的神经元。这项工作将为未来的操作确定HVC干细胞的位置，并提供更普遍的增殖区和端脑之间的地形关系的命运图。首次综合分析成人形成的声音控制神经元结构和电生理特性也将使用逆转录病毒载体进行。形态学比较成年形成的HVC神经元和分散在端脑的新神经元将首次评估成年鸟类大脑产生和整合多种神经元类别的自然潜力。成人形成的HVC前运动神经元的功能特性（通过逆转录病毒标记的绿色荧光蛋白可视化）和突触输入的来源将通过组织切片的电生理刺激记录工作来识别，作为了解这些细胞如何整合到大脑中的一步。总的来说，这项工作将测试细胞替换和鸣叫之间的关系，提供关于鸟类大脑产生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基础，旨在测试抑制替换对习得发声行为的功能后果。

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.