Advanced microscopy and behavioural approaches to study neurocircuitry and CNS function

人体防御系统的核心是免疫反应，它是对包括细菌、寄生虫和病毒在内的病原体的反应。免疫系统中的关键分子已经得到了很好的研究，并且已知它们是人体对病原体基本防御的重要组成部分。最近，我们了解到大脑也会对感染和病原体做出反应，并产生自己的免疫反应。这种反应是有益的和保护性的，就像身体的免疫反应一样。最初在人体免疫系统中描述的相同分子现在已经在大脑中被发现，并且对大脑的免疫反应很重要。很长一段时间以来，我们认为大脑不受免疫系统的影响，但事实上，在大脑的免疫反应过程中，不仅免疫分子在大脑中产生，其中一些分子一直存在于大脑中。我们正在了解到，这些分子可能在我们如何思考和学习方面发挥着重要作用。在这个提议中，我们需要设备来监测免疫系统改变的小鼠的日常活动和喂养模式。此外，我们需要一个显微镜分析系统，使我们能够精确地绘制发育过程中大脑解剖结构的变化。这些工具是最先进的系统，将行为神经科学和神经解剖学的当前方法提升到一个新的水平。这些系统的可用性将为下一代科学家提供独特和创新的培训机会，并将为他们提供目前在加拿大神经科学培训项目中无法获得的复杂知识。目前，很少有研究小组能够将行为结果直接与潜在的神经回路联系起来——支持我们的建议将在这一研究领域取得重大进展，并将帮助我们了解免疫系统状态的变化如何影响大脑的发育，以及大脑线路如何发生变化。

Central to the body's defence system is the immune response, triggered in response to pathogens including bacteria, parasites, and viruses. Key molecules in the immune system have been well studied and are known to be an important componet of the body's basic defences to pathogens. Recently, we have learned that the brain also responds to infection and pathogens and mounts its own immune response. This response is beneficial and protective, as is the body's immune response. The same molecules that were originally described in the body's immune system have now been identified in the brain and are important to the brain's immune response. For a long time, we thought that the brain was protected from the immune system, but in fact, not only are immune molecules produced in the brain during the brain's immune response, some of these molecules are present in the brain at all times. We are learning that these molecules may play important roles in how we think and learn. In this proposal we request equipment to monitor the daily activity and feeding patterns of mice that have altered immune systems. In addition, we request a microscope analysis system that will allow us to precisely map changes in brain anatomy that occurs during development. These tools are state-of-the-art systems that take current methods in behavioural neuroscience and neuroanatomy to the next level. The availability of these systems will provide unique and innovative training opportunities for the next generation of scientists and will arm them with sophisticated knowledge that is currently not available in Neuroscience training programs in Canada. Currently, there are few research groups that can directly link behavioural outcomes directly to the underlying neurocircuitry - support of our proposal will generate significant progress in this area of research and will help us understand how changes in the state of the immune system influence the development of the brain and how changes may occur in brain wiring.