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：在老鼠的大脑中大约有1000万个，在我们的大脑中大约有900亿个。这种集体活动被称为神经代码。我们破译这种密码的能力非常有限，主要是因为我们只能读取其中的一小部分。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。今年在美国出现的一种新技术，光珠显微镜，允许我们同时记录的神经元数量大幅增加：一百万个神经元这种显微镜是在纽约的洛克菲勒大学开发的，下一步将部署在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，让他们进行、试验或观察实验，这在一年前是不可能的。光珠显微镜是一种特别强大的双光子成像技术。传统的双光子显微镜将激光聚焦在大脑中的一个点上，然后沿着一个平面移动这个点，揭示那个平面上神经元的活动。如果需要体积，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，在平面内和跨平面移动所需的时间比对点成像所需的时间长得多，因此浪费了大部分成像时间。而在光珠显微镜中，光以微小间隔间隔的一行光珠形成图案，因此当显微镜扫描一个点时，它会对它下面的一整行进行成像。通过扫描单个平面，显微镜可以获得整个体积，没有浪费时间。这项技术需要三个组成部分的结合。第一个是一个专门的强大的光脉冲源，非常短暂和频繁。第二个是一个模块，它顺序地将这些脉冲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。我们已经通过单独的资金获得了第二和第三个项目，并在这里申请资金购买第一个项目，即光源。有了这个光源，我们将获得一个独特的先进的新显微镜，将允许前所未有的测量活大脑中~ 100万个神经元的活动。在更高的放大倍率下，显微镜还将提供前所未有的更小结构的大脑活动测量，例如揭示单个神经元的整个范围的活动。

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.