Cellular and synaptic rules enabling vocal communication

描述（由申请人提供）：NIDCD的一个主要目标是研究“正常和障碍沟通中的感觉运动处理”。然而，调解声音交流的具体机制尚不清楚。在这个提议中，我直接使用鸣鸟（斑胸草雀）作为模型系统来解决这些问题。这项提议的重点是HVC，一种类似于人类运动皮层的前脑结构。许多方法将应用于HVC的研究，目的是阐明控制该细胞核功能的细胞和突触规则，以便更好地了解其功能，并最终阐明人类交流障碍。第一个具体目标将解决HVC在为歌曲系统提供计时信息方面的重要性。在初步研究中，我使用了热电装置来改变歌唱斑胸草雀体内HVC的温度，从而改变了歌唱的持续时间。冷却HVC导致唱歌变慢；加热HVC加速歌曲。我将把这些研究扩展到RA （HVC的下游靶点），以便直接测试HVC是否在歌曲系统中充当自主时钟。第二个具体目标将解决有助于HVC模式生成的细胞机制。提出的实验将阐明终止HVC爆发的细胞和/或突触机制，导致核内稀疏的、特征选择性的神经元活动。第三个具体目标将解决有助于HVC中模式生成的电路机制。人们对控制HVC突触连接的规则几乎一无所知。我将记录成对的HVC细胞，研究控制HVC突触的静态和动态特性。这些实验将有助于更好地理解HVC的功能原理和地形组织。相关性：语音交流是人类互动的一个基本特征，但人们对语音产生背后的细胞和突触机制知之甚少。我的实验将集中在这些问题上，使用斑胸草雀，一个模型系统能够产生学习发声与人类有几个惊人的相似之处。这些研究可能与理解认知和语言缺陷的机制有关，如自闭症、口吃和非流利性失语症。

DESCRIPTION (provided by applicant): A principle aim of the NIDCD is the study of the "sensorimotor processing in normal and disordered communication." However, the specific mechanisms which mediate vocal communication are poorly understood. In this proposal, I directly address these issues using the songbird (zebra finch) as a model system. The proposal focuses on HVC, a forebrain structure analogous to motor cortex in humans. A number of methods will be applied to the study of HVC, with the goal of elucidating cellular and synaptic rules that govern the function of that nucleus in order to better understand its function and to ultimately shed light into disorders in human communication. The first specific aim will address the importance of HVC in providing the song system with timing information. In preliminary studies, I have used a thermoelectric device to alter the temperature of HVC in the singing zebra finch, which results in a modification of song duration. Cooling HVC leads to slower singing; heating HVC speeds the song. I will extend these studies into RA (the downstream target of HVC) in order to directly test whether HVC acts as an autonomous clock within the song system. The second specific aim will address the cellular mechanisms that contribute to pattern generation within HVC. The proposed experiments will elucidate the cellular and/or synaptic mechanisms that terminate HVC bursts, leading to sparse, feature-selective neuronal activity within that nucleus. The third specific aim will address the circuit mechanisms that contribute to pattern generation within HVC. Almost nothing is known about the rules that govern HVC synaptic connections. I will record from pairs of HVC cells to study the static and dynamic properties governing HVC synapses. These experiments will allow for a better understanding of the functional principles and topographic organization of HVC. Relevance: Vocal communication is an essential feature of human interaction, but the cellular and synaptic mechanisms that underlie speech production are poorly understood. My experiments will focus on these issues using the zebra finch, a model system capable of producing learned vocalizations with several striking parallels to humans. These studies are likely to be relevant for understanding the mechanisms of cognitive and language deficits such as autism, stuttering, and nonfluent aphasia.