Imaging the engram in mice

小鼠印迹成像

• 批准号: RGPIN-2015-04514
• 负责人: Josselyn, Sheena
• 金额: $ 5.52万
• 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: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691968
• 关键词: Imaging; engram; mice

In a human brain, 85 billion nerve cells communicate via trillions of connections using complex patterns of electrical jolts and more than 100 different chemicals. One way to understand how this complex system works is to "watch" it while it performs its normal functions. That is, one way to understand how the brain encodes and stores information is to examine neural function in real time while an animal performs a memory task.***In the 1890s, the pioneering neuroscientist, Santiago Ramón y Cajal, microscopically examined human brain cells and wrote of massively interconnecting webs of tightly packed cells, which he described as "impenetrable jungles where many investigators have lost themselves". Since that time, however, there have been numerous advances in microscopy which now allow researchers to examine rodent brain function "at the speed of thought". ***Previously neuronal activity has been assessed using in vivo electrophysiological techniques in which electrodes or wires were implanted into the brain and activity of handfuls of neurons recorded while an animal is behaving some sort of task. Although this technique offered many important insights into how brain activity correlates with behaviour, it was difficult to determine exactly which neuron was firing. The next innovation allowed researchers to literally see into the brain and monitor neuronal firing by using rodents expressing genetically-encoded calcium indicators (which fluoresce upon neural activation) and using 2-photon microscopy. This approach can be well-suited for examining the activity of neurons on the surface of the brain, but requires that the animal be restrained (head-fixed to an immovable microscope), which likely also stresses the animal. In contrast, the proposed mini-microscope, which is small enough to be mounted on the head of a mouse will make it possible to "watch" brain cell activity and while the mouse freely-behaves. This mini-microscope, though, will enable chronic recording of neural activity while an animal is performing some sort of task (memory test, social interaction, or other behaviour) without inducing stress. *** ***We believe that this visionary technology will enable researchers to stimulate one brain region and record the neural consequences in several other brain regions at the same time. This will allow us to understand not only how small portions of neurons within a brain region function, but how the brain functions overall. This technology will allow us to create a dynamic map of the brain which is crucial to understanding brain function.**

在人脑中，850亿个神经细胞通过使用复杂的电击模式和100多种不同的化学物质，通过数万亿个连接进行通信。理解这个复杂系统如何工作的一种方法是，在它执行其正常功能时“观察”它。也就是说，了解大脑如何编码和存储信息的一种方法是，在动物执行记忆任务时实时检查神经功能。19世纪90年代，神经学家先驱圣地亚哥·拉蒙·卡哈尔对人类脑细胞进行了显微镜检查，并描述了紧密堆积的细胞组成的大规模相互连接的网络，他将这些细胞描述为“许多研究人员迷失了自我的难以穿透的丛林”。然而，从那时起，显微镜技术取得了许多进步，现在研究人员可以“以思维的速度”检查啮齿动物的大脑功能。*之前，人们使用活体电生理技术来评估神经元的活动，这些技术将电极或电线植入大脑，并在动物执行某种任务时记录少量神经元的活动。虽然这项技术提供了许多关于大脑活动如何与行为相关的重要见解，但很难准确地确定哪个神经元在放电。下一项创新使研究人员能够真正看到大脑，并通过使用表达遗传编码的钙指示器(在神经激活时会发出荧光)的啮齿类动物和使用双光子显微镜来监测神经元的放电。这种方法可以很好地适合于检查大脑表面神经元的活动，但要求动物受到约束(头部固定在固定的显微镜下)，这可能也会给动物带来压力。相比之下，拟议中的微型显微镜，它足够小，可以安装在小鼠的头上，使其能够在小鼠自由活动的同时“观察”脑细胞的活动。然而，这种迷你显微镜将能够在动物执行某种任务(记忆测试、社会互动或其他行为)时长期记录神经活动，而不会产生压力。*我们相信，这项富有远见的技术将使研究人员能够刺激一个大脑区域，同时记录其他几个大脑区域的神经后果。这将使我们不仅了解大脑区域内的一小部分神经元是如何运作的，而且了解大脑整体是如何运作的。这项技术将允许我们创建大脑的动态地图，这对了解大脑功能至关重要。**