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

大脑功能最显著的输出是行为，但神经系统是如何产生行为的还不是很清楚，很大程度上是因为脊椎动物行为背后的大多数神经通路是复杂的。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实验室先前开发的技术。传统上，行为神经通路中的信号被认为是单向流动的，从上游的指挥中心到大脑中的输出站，该输出站激活产生行为的肌肉。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也会回流到大脑内的指挥中心。据推测，反馈信号在塑造动物的行为中起着重要作用。在本研究中，反馈信号的功能角色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，并可能阐明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之外，该项目还将被用作培训来自不同背景的学生（包括代表性不足的少数民族）在神经科学领域的机会。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）的中央声音网络，可以详细研究大脑活动中的动态组织。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向后投射到运动前核的神经元群进行细胞分析。光遗传学工具在非洲爪蟾等非遗传模式生物中的应用尚处于起步阶段。该项目的目标之一是完善这项技术，使其能够被更广泛的比较神经科学家所利用。该研究结果不仅将提供对细胞水平上功能行为的节律产生神经网络的结构和功能的深入了解，而且还可能揭示神经网络中反馈回路对产生稳定的神经元节律的潜在重要性。节律性神经元活动并不局限于运动系统，而是普遍存在于整个中枢神经系统，并被认为是感知和认知等重要功能的基础。因此，理解控制节律产生的生物物理原理，使用一个简单的神经网络，有可能阐明一般神经元振荡的机制。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.