Recording from one million neurons

大脑的功能是通过无数神经元的集体活动来组织的：老鼠的大脑中大约有1000万个神经元，而我们的大脑中大约有900亿个神经元。这种集体活动被称为神经密码。我们破译这些密码的能力非常有限，很大程度上是因为我们只能接触到其中的一小部分。当今最好的技术允许我们一次最多读取几千个神经元的活动。今年在美国出现了一项新技术，光珠显微镜，可以使我们同时记录的神经元数量大幅增加：100万个神经元。这台显微镜是由纽约洛克菲勒大学开发的，接下来将被部署到美国各地的重点实验室。由于我们与发明者的密切合作，我们有机会在美国以外部署第一个这样的设备。我们将把它安装在我们在伦敦的实验室里，在那里我们将为英国各地的同事提供充足的机会来进行、试验或观察实验，这些实验在一年前是不可能的。光珠显微镜是双光子成像技术的一个特别强大的版本。传统的双光子显微镜将来自激光的光聚焦在大脑的一个点上，并沿着一个平面移动这个点，揭示该平面上神经元的活动。如果需要一个体积，则必须在多个平面上重复采集，这极大地限制了采集速率。此外，在一个平面内移动和跨平面移动所需的时间比成像一个点所需的时间要长得多，因此大部分成像时间都被浪费了。相反，在光珠显微镜中，光被排列成一串珠子，在时间上以极小的间隔分开，所以当显微镜扫描一个点时，它正在对它下面的整条线进行成像。通过扫描单个平面，显微镜获得了整个体积，没有浪费时间。该技术需要三个组件的组合。第一种是一种特殊的强大光脉冲源，这种光脉冲非常短暂和频繁。第二个是一个模块，它将这些脉冲依次聚焦成一排在空间和时间上分开的“光珠”。第三种是传统的双光子显微镜，通过水平面扫描这条线。由于有单独的资金，我们已经获得了第二和第三个项目，现在我们正在申请资金来购买第一个项目，即光源。有了这个光源，我们将获得一种独特先进的新型显微镜，它将允许对活大脑中约100万个神经元的活动进行前所未有的测量。在更高的放大倍数下，显微镜还将提供前所未有的对更小结构的大脑活动的测量，例如揭示单个神经元整个范围的活动。

Brain function is organized through the collective activity of a myriad neurons: about 10 million of them in a mouse brain, and about 90 billion in our brain. This collective activity is called the neural code. Our ability to decipher this code is very limited, largely because we have been able to access only small fragments of it. The best technologies available today allow us to read at most the activity of a few thousand neurons at a time.A new technology that appeared in the USA this year, the Light Beads Microscope, allows for a major increase in the number of neurons that we can record at the same time: one million neurons. This microscope was developed at Rockefeller University in New York, and will next be deployed in key laboratories across the United States. Thanks to our close collaboration with the inventors, we have the opportunity to deploy the first such device outside the USA. We will install it in our laboratory in London, where we will provide ample access to colleagues across the United Kingdom to perform, pilot, or observe experiments that would not have been possible even a year ago. The Light Beads Microscope is a particularly powerful version of a technology called two-photon imaging. A traditional two-photon microscope focuses light from a laser on a single point in the brain and moves this point along a plane, revealing the activity of the neurons in that plane. If a volume is desired, the acquisition must be repeated across multiple planes, greatly limiting the rate of acquisition. Moreover, the time required to move within a plane and across planes is much longer than the time required to image a point, so most of the imaging time is wasted. In a Light Beads Microscope, instead, the light is patterned in a line of beads separated in time by minuscule intervals, so while the microscope is scanning one point, it is imaging an entire line below it. By scanning a single plane, the microscope acquires a whole volume, with no wasted time. This technology requires a combination of three components. The first is a specialized source of powerful light pulses that are extraordinarily brief and frequent. The second is a module that sequentially focuses these pulses into a line of "light beads" separated in both space and time. The third is a traditional two-photon microscope that scans this line through a horizontal plane. We have already secured the second and third items thanks to separate funding, and are here requesting funds to purchase the first item, the light source. With this light source, we will obtain a uniquely advanced new microscope that will allow unprecedented measurements of the activity of ~1 million neurons in the living brain. At higher magnification, the microscope will also provide unprecedented measurements of brain activity in smaller structures, for instance to reveal the activity of the entire extent of a single neuron.