Genetic Analysis of Neuromuscular Synaptic Structure and Function

神经肌肉突触结构和功能的遗传分析

• 批准号: RGPIN-2018-06064
• 负责人: Stewart, Bryan
• 金额: $ 2.33万
• 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=665954
• 关键词: Genetic; Analysis; Neuromuscular; Synaptic; Structure

***Understanding how the brain works has fascinated human kind for centuries. The brain provides some of the most fascinating scientific questions that, even today, remain far from being answered, such as: How do we learn? How do we remember? The diseased brain remains equally puzzling and some of the most troubling afflictions – neurodegenerative disease such as Alzheimer's, Parkinson's, as well as mental health disorders such as schizophrenia and depression - arise when normal brain function is disrupted.***Neurons are the cells of the nervous system that sense, process and communicate information. They are the cells that respond to pain and they activate muscles to move away from pain. They are the cells that participate in circuits that encode our memories and allow us to learn. Thus, if we are ultimately to understand brain function, it is critically important that we understand how the individual cells within the brain work and what happens to them when they are diseased. This basic approach will lead to a fundamental understanding of brain function and will identify therapeutic approaches to the diseased brain.***One of the most important tasks that neurons perform is to regulate their function in the face of diverse challenges. These challenges include their own growth, environmental challenges, and disease states. Neurons must respond in a way that preserves their function within a defined physiological range. Individual nerve cells should neither be excessively active nor should they be abnormally inactive. This balance must be preserved to maintain the robust function of neural circuits throughout life. The long-term goal of my research program is to therefore understand the mechanisms that contribute to establishing and maintaining synaptic function. We pay particular attention to the relationship between synaptic structure and physiology and the way in which development and function are inter-related. ***To address such issues my research team combines the classical and molecular genetics of the fruit fly, Drosophila melanogaster, with developmental analysis and measurements of physiology. Our basic approach is to use genetics to perturb genes in a systematic way and then determine how the nerve cells respond to understand their basic function. In doing so we generate new knowledge that advances our understanding of the neural control of behaviour and will help is to predict what happens when the brain is not healthy.********

** 了解大脑如何工作已经吸引了人类几个世纪。大脑提供了一些最吸引人的科学问题，即使在今天，这些问题仍然远未得到解答，例如：我们如何学习？我们怎么记得？患病的大脑仍然同样令人困惑，一些最令人不安的痛苦-神经退行性疾病，如阿尔茨海默氏症，帕金森氏症，以及精神健康障碍，如精神分裂症和抑郁症-当正常的大脑功能被破坏时就会出现。神经元是神经系统中感知、处理和交流信息的细胞。它们是对疼痛做出反应的细胞，它们激活肌肉以远离疼痛。 它们是参与编码我们的记忆并允许我们学习的电路的细胞。因此，如果我们最终要了解大脑的功能，我们必须了解大脑中的单个细胞是如何工作的，以及当它们患病时会发生什么。这种基本方法将导致对大脑功能的基本了解，并将确定患病大脑的治疗方法。*神经元执行的最重要的任务之一是在面对各种挑战时调节其功能。这些挑战包括自身的成长、环境挑战和疾病状态。神经元必须以一种在限定的生理范围内保持其功能的方式做出反应。单个神经细胞既不应过度活跃，也不应异常不活跃。这种平衡必须保持，以维持整个生命神经回路的强大功能。因此，我的研究计划的长期目标是了解有助于建立和维持突触功能的机制。我们特别关注突触结构和生理之间的关系，以及发育和功能相互关联的方式。* 为了解决这些问题，我的研究团队将果蝇（Drosophila melanogaster）的经典和分子遗传学与发育分析和生理测量相结合。我们的基本方法是使用遗传学以系统的方式干扰基因，然后确定神经细胞如何响应以了解它们的基本功能。在这样做的过程中，我们产生了新的知识，促进了我们对行为神经控制的理解，并将有助于预测当大脑不健康时会发生什么。