Functional analyses of the vocal central pattern generators of African clawed frogs

非洲爪蛙发声中枢模式发生器的功能分析

• 批准号: 1934386
• 负责人: Ayako Yamaguchi
• 金额: $ 90万
• 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: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1934386&HistoricalAwards=false
• 关键词: Functional; analyses; vocal; central; pattern

The most salient output of brain function is behavior, but how the nervous system produces behavior is not well understood, largely because most of the neural pathways underlying behavior in vertebrates are complicated. In this research project, the vocal behavior of African clawed frogs is used as a model because their vocal neural pathways are simple, straight forward, and accessible using techniques previously developed in the PI's laboratory. Traditionally, the signal within behavioral neural pathways has been considered to flow in one direction, from the upstream command center to the output station in the brain that activates muscles that generate behavior. However, the investigators recently obtained evidence that, in addition to activating muscles, the neuronal signal from the output station also flows back to the command center within the brain. It is hypothesized that the feedback signal plays an important role in shaping the behavior of animals. In this study, functional roles of the feedback signal will be examined using a variety of experimental techniques. The results of the study will provide us with an understanding of how behaviors are generated in general, and may shed light on the importance of feedback signal for behavioral neural circuitry in general. In addition to the significance of the scientific outcomes, the project will be used as an opportunity to train students from diverse backgrounds, including under-represented minorities, in the field of neuroscience. A major goal in neuroscience is to understand 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 central vocal network of African clawed frog, Xenopus laevis, allows detailed investigation of the dynamic organization of the brain in action. In this study, the investigators will carry out cellular analyses of the newly discovered population of neurons that projects back from the motor nucleus to the premotor nucleus using electrophysiological and optogenetic approaches. The application of optogenetic tools to non-genetic model organisms such as Xenopus laevis is still in its infancy. One of the goals of the project is to perfect the technique so that it can be utilized by a broader community of comparative neuroscientists. The results of the study will not only provide insight into the structure and function of the rhythm-generating neural network underlying functional behavior at the cellular level, but also may reveal the potential importance of a feedback loop within a neural network to generate stable neuronal 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.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

大脑功能最突出的输出是行为，但神经系统如何产生行为还没有得到很好的理解，主要是因为脊椎动物行为背后的大多数神经通路都很复杂。在这个研究项目中，非洲爪蛙的发声行为被用作模型，因为它们的发声神经通路简单，直接，并且可以使用PI实验室以前开发的技术。传统上，行为神经通路中的信号被认为是单向流动的，从上游的命令中心到大脑中激活产生行为的肌肉的输出站。然而，研究人员最近获得的证据表明，除了激活肌肉外，来自输出站的神经元信号还流回大脑内的指挥中心。据推测，反馈信号在塑造动物的行为中起着重要作用。在这项研究中，反馈信号的功能作用将使用各种实验技术进行检查。这项研究的结果将使我们了解行为是如何产生的，并可能揭示反馈信号对行为神经回路的重要性。 除了科学成果的重要性外，该项目还将被用作在神经科学领域培训来自不同背景的学生的机会，包括代表性不足的少数民族。 神经科学的一个主要目标是了解神经网络如何产生行为背后的运动程序。虽然分析产生行为的完整神经网络是一项艰巨的任务，但非洲爪蟾（Xenopus laevis）的中央发声网络允许详细研究大脑的动态组织。在这项研究中，研究人员将使用电生理学和光遗传学方法对新发现的从运动核投射回运动前核的神经元群体进行细胞分析。光遗传学工具在非洲爪蟾等非遗传模式生物中的应用仍处于起步阶段。该项目的目标之一是完善这项技术，以便更广泛的比较神经科学家社区可以使用它。该研究的结果不仅将深入了解细胞水平上的功能行为背后的节律生成神经网络的结构和功能，而且还可能揭示神经网络内的反馈回路对生成稳定的神经元节律的潜在重要性。节律性神经元活动不仅限于运动系统，而且在整个CNS中普遍存在，并被认为是感知和认知等重要功能的基础。因此，了解使用简单神经网络控制节律产生的生物物理原理有可能阐明一般神经元振荡的潜在机制。该奖项反映了NSF的法定使命，并且通过使用基金会的知识价值和更广泛的影响进行评估，被认为值得支持。审查标准。

项目成果

Ex vivo brain preparation to Analyze vocal pathways of Xenopus frogs.

离体大脑准备分析爪蟾的声音通路。

• DOI: 10.1101/pdb.prot106872
• 发表时间: 2021
• 期刊: Cold Spring Harbor protocols
• 作者: Yamaguchi, Ayako

Molecular characterization of frog vocal neurons using constellation pharmacology

使用星座药理学对青蛙发声神经元进行分子表征

• DOI: 10.1152/jn.00105.2020
• 发表时间: 2020
• 期刊: Journal of Neurophysiology
• 影响因子: 2.5
• 作者: Inagaki, Ryota Thomas;Raghuraman, Shrinivasan;Chase, Kevin;Steele, Theresa;Zornik, Erik;Olivera, Baldomero M;Yamaguchi, Ayako
• 通讯作者: Yamaguchi, Ayako