Neurogenic plasticity and brain development

神经源性可塑性和大脑发育

• 批准号: RGPIN-2016-06325
• 负责人: Tropepe, Vincent
• 金额: $ 2.77万
• 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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=667168
• 关键词: Neurogenic; plasticity; brain; development

The production of new neurons in the brain, a process called neurogenesis, continues throughout life. This is made possible by the existence of small populations of stem cells that persist in defined regions of the brain (called stem cell niches) that undergo cell division to produce new neurons functionally integrating into existing neural circuits. Research over the last 20 years has shown that neurogenesis in the mature brain is not a passive process, but instead can be modified with respect to the rate of stem cell division, the type of new neurons produced, or the extent to which new neurons survive. This form of structural plasticity, referred to here as ‘neurogenic plasticity,' is thought to depend on mechanisms that are intrinsic to the brain interacting with the animal's environment. However, our understanding of this interaction is quite limited and this represents a topic of intense interest in the field. Our research investigates how an animal's external environment influences neurogenesis in the brain and whether this affects behaviour.***The long-term objective of our NSERC-funded research is to use zebrafish to gain novel insight into the molecular and cellular basis of environment-induced neurogenic plasticity in the brain. To accomplish this objective, we have developed a research proposal that will address three experimental aims. First, we will explore how altering visual cues can modify neurogenesis in distinct stem cell niches in the brain. By utilizing genetic methods, we can trace when new neurons are born, what part of the brain they originate from, and identify the type of neuron they become. We will perform these experiments under standard environmental conditions as well as visually altered environments to determine how sensory input affects neurogenesis. Second, we will examine the impact that a change in sensory environment has on behaviour and whether neurogenesis itself is necessary for these effects. A digital tracking system will be used to see if vision-dependent movement is affected as animals experience an altered visual environment, and genetic methods will be used to specifically block neurogenesis to see if this has the same effect on behaviour. Finally, using both genetic and genomic technologies, we will investigate the extent to which different molecular signalling pathways serve as mechanistic links that modify neurogenesis output in response to a changing visual environment.***Our research will elucidate mechanisms of experience induced neurogenic plasticity for a deeper understanding of the fundamental relationship between the environment, brain structure, and behaviour. Beyond developmental neuroscience, our work will have broad implications for other fields of research with a focus on animal-environment interactions, such as behavioural ecology, cognitive neuroscience, and neural repair and rehabilitation.**

大脑中新神经元的产生，一个被称为神经发生的过程，贯穿一生。这是由于存在少量的干细胞，这些干细胞持续存在于大脑的特定区域（称为干细胞龛），这些干细胞经历细胞分裂以产生功能上整合到现有神经回路中的新神经元。过去20年的研究表明，成熟大脑中的神经发生不是一个被动的过程，而是可以在干细胞分裂的速度、产生的新神经元的类型或新神经元存活的程度方面进行修改。这种形式的结构可塑性，在这里被称为“神经源性可塑性”，被认为取决于大脑与动物环境相互作用的内在机制。然而，我们对这种相互作用的理解是相当有限的，这代表了该领域的一个非常感兴趣的话题。我们的研究调查了动物的外部环境如何影响大脑中的神经发生，以及这是否会影响行为。我们NSERC资助的研究的长期目标是利用斑马鱼获得新的见解，以了解大脑中环境诱导的神经可塑性的分子和细胞基础。为了实现这一目标，我们已经制定了一项研究计划，将解决三个实验目标。首先，我们将探讨如何改变视觉线索可以修改在不同的干细胞在大脑中的壁龛神经发生。通过利用遗传学方法，我们可以追踪新神经元何时诞生，它们来自大脑的哪个部分，并识别它们成为的神经元类型。我们将在标准环境条件下以及视觉改变的环境下进行这些实验，以确定感觉输入如何影响神经发生。其次，我们将研究感觉环境的变化对行为的影响，以及神经发生本身是否是这些影响所必需的。一个数字跟踪系统将被用来观察当动物经历一个改变的视觉环境时，视觉依赖的运动是否会受到影响，遗传方法将被用来专门阻止神经发生，看看这是否对行为有同样的影响。最后，使用遗传和基因组技术，我们将研究不同的分子信号通路在多大程度上作为机制链接，修改神经发生输出响应不断变化的视觉环境。我们的研究将阐明经验诱导的神经可塑性的机制，以更深入地了解环境，大脑结构和行为之间的基本关系。除了发育神经科学，我们的工作将对其他研究领域产生广泛的影响，重点是动物与环境的相互作用，如行为生态学，认知神经科学，神经修复和康复。