Dissecting the mechanisms of neural circuit maturation that underpin behavioral development using zebrafish

使用斑马鱼剖析支持行为发展的神经回路成熟机制

• 批准号: RGPIN-2021-03866
• 负责人: Koyama, Minoru
• 金额: $ 2.4万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744899
• 关键词: Dissecting; mechanisms; neural; circuit; maturation

All animals are born with a set of reflexive behaviours that ensure their immediate survival. As animals mature, they become capable of increasingly sophisticated behaviours. Addressing the underlying mechanisms of circuit maturation in the brain is essential to understanding how neural circuits develop, are functionally organized, and operate. Despite tremendous progress in our knowledge about early brain formation and the function of mature brains, very little is known about the relationship between brain maturation and behavioural development. Gaining insights into this relationship has been difficult due to the necessity to study both the formation and function of increasingly complex emerging circuits as they dynamically integrate with existing motor control circuitry. This research is especially challenging in mammalian models that present formidable technical hurdles due to the scale and complexity of the brain. My laboratory tackles this challenge using larval zebrafish, a powerful vertebrate model system used for studying both the formation and function of the brain. The larval zebrafish provides excellent genetic and optical access, and develops a rich set of behaviours within a few days after birth. Furthermore, its brain is vastly more compact than mammalian models despite having a well-conserved vertebrate brain architecture. Thus, this organism makes it possible to genetically label specific sets of developing neurons and optically monitor how they become integrated into circuits and ultimately contribute to behaviour. Using this strategy, my research has previously revealed fundamental brain organization principles that underlie the expansion of motor outputs observed during early behavioural development. In this proposal, we aim to reveal circuit mechanisms that facilitate an animal's ability to produce flexible movement sequences at later stages of behavioural development. Specifically, we will perform in-depth analyses of the neuronal circuits involved in sequential locomotor behaviour using cutting-edge optical and genetic techniques. Through this research, we aim to reveal the brain mechanisms that enable integration and flexible recruitment of new circuit components without compromising existing components. This research has the potential to provide insights that will guide the development of artificial intelligence and robotics technologies that enable interaction with the external world through flexible sequences of actions.

所有动物出生时都有一套反射性行为，以确保它们立即生存。随着动物的成熟，它们变得能够进行越来越复杂的行为。解决大脑回路成熟的潜在机制对于理解神经回路如何发展、功能组织和运作至关重要。尽管我们对早期大脑形成和成熟大脑功能的认识取得了巨大进展，但对大脑成熟和行为发育之间的关系知之甚少。深入了解这种关系一直很困难，因为有必要研究日益复杂的新兴电路的形成和功能，因为它们与现有的电机控制电路动态集成。这项研究在哺乳动物模型中尤其具有挑战性，由于大脑的规模和复杂性，这些模型存在巨大的技术障碍。 我的实验室使用斑马鱼幼体来应对这一挑战，这是一种用于研究大脑形成和功能的强大脊椎动物模型系统。斑马鱼幼鱼提供了极好的遗传和光学途径，并在出生后几天内发展出一套丰富的行为。此外，它的大脑比哺乳动物模型要紧凑得多，尽管它有一个保存良好的脊椎动物大脑结构。因此，这种生物体使得有可能在遗传上标记发育中的特定神经元，并通过光学方法监测它们如何整合到电路中并最终对行为做出贡献。使用这种策略，我的研究以前揭示了基本的大脑组织原则，这些原则是在早期行为发展过程中观察到的运动输出扩展的基础。在这项提案中，我们的目标是揭示电路机制，促进动物的能力，以产生灵活的运动序列在行为发展的后期阶段。具体来说，我们将使用尖端的光学和遗传技术对参与顺序运动行为的神经元回路进行深入分析。通过这项研究，我们的目标是揭示大脑机制，使新的电路组件的整合和灵活的招聘，而不损害现有的组件。这项研究有可能提供见解，指导人工智能和机器人技术的发展，通过灵活的动作序列与外部世界进行交互。