A telencephalic pattern generator for song

描述（由申请人提供）：鸟歌是理解复杂声音行为（如人类语言）的神经基础的绝佳模型。鸣禽自然地学习和发出它们的歌声，就像人类说话一样，学习过程依赖于听觉。我们的长期目标是了解歌曲产生的神经机制。首先，该提案考虑了斑胸草雀中端脑核HVc所起的作用，斑胸草雀一生中都会发出一种高度定型的歌曲。HVc可能参与推动歌曲的产生：它是歌唱所必需的，它的神经元在歌曲产生过程中显示出前运动和模式活动，并且在解剖学上它可以影响鸣管（鸟类的发声器官）的输出。此外，对体内HVc的研究表明，它是歌曲的模式发生器。本文描述的实验建议开发一种HVc切片制剂，该制剂可以在体外诱导产生活性，模仿体内歌曲产生过程中观察到的节律性活动。最近的间接证据表明，在HVc的脑切片制剂中可以引发模式活动；这里的目标是直接观察尖峰活动，并可靠地诱导它。具体来说，细胞外记录将用于监测体外HVc细胞对短暂高频刺激、神经调节剂应用或两者的响应的尖峰模式。如果有模式活动的结果，我们将分析它的刻板印象和相似的鸟的歌声，从大脑切片。该提议具有很强的探索性，因为它旨在发现在体外诱导HVc中有节奏的、与唱歌相关的活动的条件。这种方法至少将阐明HVc能够在多大程度上孤立地产生节律性活动。如果这些实验产生了与歌曲相关的可靠的节奏活动，那么这将是一个强有力的候选“模拟歌唱”的准备。这样的准备将提供为数不多的体外模式生成的脊椎动物实例之一，声称是端脑内声音行为的体外模式生成的第一个实例，并且它将为未来HVc节奏活动的机制研究，歌曲产生，更广泛地说，是对序列和模式运动输出的运动控制的基础。这些知识将适用于理解控制人类语言产生的机制，并增强对语言的理解，它是如何学习的，以及它的病理。

DESCRIPTION (provided by applicant): Birdsong is an excellent model for understanding the neural basis of complex vocal behavior, like human speech. Songbirds naturally learn and produce their song, and like human speech, the learning process depends on hearing. Our long-term goal is to understand the neural mechanisms of song production. As a beginning, this proposal considers the role played by the telencephalic nucleus HVc in zebra finches, which produce one song with high stereotypy throughout life. HVc is likely to participate in driving song production: it is required for singing, its neurons display premotor and patterned activity during song production, and it is poised anatomically to influence the output of the syrinx, the avian vocal organ. Furthermore, studies of HVc in vivo have implicated it as a pattern generator for song. The experiments described here propose to develop a slice preparation of HVc that can be induced to produce activity in vitro that mimics the rhythmic activity observed during song production in vivo. Recent indirect evidence shows that patterned activity can be elicited in brain slice preparations of HVc; the goal here is to directly observe the spiking activity, and to induce it reliably. Specifically, extracellular recordings will be used to monitor the spiking patterns of HVc cells in vitro in response to brief high frequency stimuli, application of neuromodulators, or both. If patterned activity results, we will analyze it for stereotypy and similarity to the song of the bird from which the brain slice was made. The proposal is highly exploratory because it aims to discover the conditions under which rhythmic, singing-related activity can be induced in HVc in vitro. This approach will at least clarify the extent to which HVc is capable of generating rhythmic activity in isolation. If these experiments yield reliable rhythmic activity related to song, then this will be a strong candidate for a preparation of "fictive singing." Such a preparation would provide one of the few vertebrate examples of pattern generation in vitro, claim the first instance of in vitro pattern generation for vocal behavior within the telencephalon, and it would form a basis for future mechanistic investigations of rhythmic activity in HVc, song production, and more generally the motor control of sequenced and patterned motor outputs. This knowledge would be applicable to understanding the mechanisms governing speech production in humans, and enhance the understanding of speech, how it is learned, and its pathologies.