Mechanisms of experience-dependent hippocampal neurogenesis

经验依赖性海马神经发生机制

• 批准号: RGPIN-2022-04174
• 负责人: Fernandes, Karl
• 金额: $ 2.48万
• 依托单位: Université de Sherbrooke
• 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=760585
• 关键词: Mechanisms; experience; dependent; hippocampal; neurogenesis

This research program investigates how the brain is shaped by life experiences. Indeed, it has been known for over half a century that the brain's anatomy, chemistry, and function are powerfully influenced by experiences such as stress, physical activity, and cognitive training. The ability of the brain to be shaped by experience is called plasticity, and it is one of the brain's defining features. Understanding how this occurs will help us understand key brain functions, such as the ability to learn and remember. Our long-term goal is to develop an integrated model, from life experiences to gene, of how life experience regulates brain plasticity. We focus on the hippocampus, one of the rare regions of the adult brain that is capable of neurogenesis (the process by which brain stem cells produce new brain cells). Remarkably, hippocampal neurogenesis can be measurably changed simply by placing mice in different housing environments that are enriched with a running wheel, social interactions and/or stressors. This discovery serves as a model for the fundamental questions we are pursuing here. In our prior work, we started at the behavioral level, developing housing models that allowed us to demonstrate that individual elements within an enriched environment (such as physical activity, cognitive stimulation, stress, and social interactions) affect the hippocampus in different ways. This prior work identified potential pathways by which such experiences "talk" to the brain. Based on our findings, we now propose to expand our work at the cellular and molecular levels. We will use state of the art technologies that describe how each of the thousands of cells in the hippocampus is behaving when an animal is exposed to exercise, and use advanced animal models to identify the cellular processes that are mediating these responses to exercise. This research program will generate fundamental biological insights into the mechanisms of brain plasticity, which is an essential feature of how our brains function. Importantly, this project will also provide highly qualified personnel with valuable, specialized and versatile expertise for future academic, industrial and regulatory positions.

这项研究计划调查大脑是如何由生活经历塑造的。事实上，半个多世纪以来，众所周知，大脑的解剖、化学和功能受到压力、体力活动和认知训练等经历的强烈影响。大脑被经验塑造的能力被称为可塑性，这是大脑的定义特征之一。了解这是如何发生的，将有助于我们了解关键的大脑功能，如学习和记忆的能力。我们的长期目标是开发一个从生活经验到基因的综合模型，研究生活经验如何调节大脑的可塑性。我们关注的是海马体，这是成人大脑中罕见的具有神经发生能力的区域之一(脑干细胞产生新脑细胞的过程)。值得注意的是，只要把小鼠放在不同的环境中，这些环境中充满了跑轮、社会互动和/或压力源，就可以显著改变海马神经发生。这一发现为我们在这里追寻的基本问题提供了一个模型。在我们之前的工作中，我们从行为层面开始，开发了住房模型，使我们能够证明丰富环境中的单个元素(如身体活动、认知刺激、压力和社会互动)以不同的方式影响海马体。这项先前的工作确定了这类体验与大脑“对话”的潜在途径。基于我们的发现，我们现在建议在细胞和分子水平上扩大我们的工作。我们将使用最先进的技术来描述当动物暴露在运动中时，海马体中数千个细胞的每个细胞的行为，并使用先进的动物模型来识别调节这些运动反应的细胞过程。这项研究计划将产生对大脑可塑性机制的基本生物学见解，这是我们大脑运作的一个基本特征。重要的是，该项目还将为未来的学术、工业和监管职位提供高素质的人员，提供宝贵的、专门的和多才多艺的专业知识。