Functional Analyses of the Neural Circuits Underlying Vocal Production in Xenopus Laevis

非洲爪蟾发声神经回路的功能分析

• 批准号: 1557945
• 负责人: Ayako Yamaguchi
• 金额: $ 57.65万
• 依托单位: University of Utah
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557945&HistoricalAwards=false
• 关键词: Functional; Analyses; Neural; Circuits; Underlying

The most salient output of brain function is behavior. However, how the nervous system produces behavior is not well understood, largely because most of the neural pathways underlying behavior are complicated. In this research project, vocal behavior of African clawed frogs is used as a model because their vocal neural pathways are simple and straight forward, and the pathways in action can be studied using techniques that were previously developed in the PI's laboratory. In addition to their simplicity and accessibility, the frog vocal pathways provide a unique opportunity to study how female and male brains function differently; male and female frogs produce sex-specific vocalizations during the breeding season, and the injection of male-specific hormones into an adult female results in male-like vocalizations within thirteen weeks. In this study, the focus is placed on one group of cells that are known to play a critical role in the operation of the pathways. A variety of experimental techniques will be used to understand where these neurons are, how these neurons function, and how they respond to male-specific hormones. The results of the study will not only provide us with the understanding of how behaviors are generated in the two sexes, but also provide us with an insight into how human brains generates rhythmic activity such as alpha and gamma waves, many of which are known to underlie cognitive processes, and known to be disrupted in diseased states. A fundamentally important question in neuroscience is how neural networks function to generate motor programs that underlie behavior. Although analyses of a complete neural network that generates behavior is a formidable task, the relative simplicity of the Xenopus vocal network combined with the development of the fictive preparation (a "singing brain in a dish" preparation) and the application of behavioral, electrophysiological, anatomical, and newly developed optogenetic techniques allows detailed investigation of the dynamic organization of brain in action. The results of the proposed study will not only provide insight into the structure, function, and plasticity of the rhythm-generating neural network at the cellular levels, but also allow us to understand the logic of how a feedback loop should be engineered into a network to generate stable rhythms. Rhythmic neuronal activity is not limited to motor systems, but is prevalent across the entire CNS and is considered to underlie important functions such as perception and cognition. Thus, understanding the biophysical principles that govern rhythm generation using a simple neural network has a potential to elucidate mechanisms underlying neuronal oscillations in general. On a technical level, successful application of optogenetic tools to the Xenopus fictive preparation in vitro fills an important gap between research efforts conducted on genetic vs non-genetic model organisms. There are many non-genetic model organisms that present unique questions. The ability to express genetically encoded tools in non-model organisms represents a revolutionary change in the field of comparative neuroscience.

大脑功能最显着的输出是行为。 然而，神经系统如何产生行为尚不清楚，很大程度上是因为大多数行为背后的神经通路都很复杂。 在这个研究项目中，使用非洲爪蛙的发声行为作为模型，因为它们的发声神经通路简单直接，并且可以使用 PI 实验室先前开发的技术来研究起作用的通路。 除了简单易懂之外，青蛙的发声通路还提供了一个独特的机会来研究雌性和雄性大脑的不同功能。雄性和雌性青蛙在繁殖季节会发出特定性别的声音，将雄性特有的激素注射到成年雌性体内会在十三周内产生类似雄性的声音。 在这项研究中，重点放在已知在通路运作中发挥关键作用的一组细胞。 将使用各种实验技术来了解这些神经元的位置、这些神经元如何发挥作用以及它们如何对男性特异性激素做出反应。 这项研究的结果不仅能让我们了解两性的行为是如何产生的，还能让我们深入了解人类大脑如何产生阿尔法波和伽马波等节律性活动，其中许多活动是认知过程的基础，并且在疾病状态下会受到干扰。 神经科学中一个根本性的重要问题是神经网络如何发挥作用来生成行为背后的运动程序。 尽管对产生行为的完整神经网络进行分析是一项艰巨的任务，但非洲爪蟾发声网络的相对简单性与虚构制剂（“盘中唱歌的大脑”制剂）的发展以及行为、电生理学、解剖学和新开发的光遗传学技术的应用相结合，可以对大脑活动的动态组织进行详细研究。 这项研究的结果不仅将深入了解细胞水平上节律生成神经网络的结构、功能和可塑性，而且使我们能够理解如何将反馈环设计到网络中以生成稳定的节律的逻辑。 节律神经元活动不仅限于运动系统，而且普遍存在于整个中枢神经系统中，并被认为是感知和认知等重要功能的基础。 因此，了解使用简单的神经网络控制节律生成的生物物理原理有可能阐明神经元振荡的一般机制。 在技​​术层面上，光遗传学工具成功应用于非洲爪蟾体外虚构制剂，填补了遗传与非遗传模型生物研究工作之间的重要空白。 有许多非遗传模式生物提出了独特的问题。 在非模型生物体中表达基因编码工具的能力代表了比较神经科学领域的革命性变化。