Nature Methods Highlights . . . Transform brain imaging techniques to record more brain neurons.

One of the main objectives of brain research is to record the dynamics of neuronal population.there are about 86 billion neurons in human brain and 71 million neurons in mouse brain.even the simplest behavior involves the interaction of a large number of neurons, so it can be said that the more neurons we record, the more accurate we explore the brain.optical imaging can provide high resolution (direct observation of a single neuron) and noninvasive (i.e. in vivo imaging without brain damage).more importantly, optical methods can record specific cell types and measure the dynamic changes of neurons.for deep brain imaging, multi photon microscopy (MPM) is the main imaging method.the two-photon microscope invented by Denk and Webb in 1990 (Science, 1990, Webb research group, now Chris Xu research group) has directly promoted the rapid development of neuroscience in the past 30 years.in 2013, Chris Xu team invented the three photon microscope (nature photonics, 2013) again, which increased the imaging depth of mouse brain from 500 μ m to more than 1500 μ m, and realized the noninvasive hippocampal imaging for the first time (nature methods, 2017; nature methods, 2018), which once again promoted the scientific research climax of neuroscience.at present, MPM usually works under the limit of photon shot noise. Therefore, on the premise of ensuring high spatial and temporal resolution, the number of neurons that can be imaged is limited by signal photons, which are determined by the maximum allowable average power and peak power of biological samples.specifically, when the average power is too high, the brain absorbs too much heat from the light source, which will lead to brain necrosis due to excessive temperature; however, when the peak power is too high, the laser at the focus will directly damage the neural structure.how to further improve the number of imaging neurons can not be achieved by simply improving the performance of light source or microscope, which is a basic problem.on December 2, 2019, Bo Li (Li Bo) and Chris Xu published an article in the journal Nature Methods: an adaptive exercise source for high speed multiphoton microscopy. The solution to the above problem is that the average power and peak power are not increased, and the number of recordable neurons is increased by more than 30 times.for example, for the cerebral cortex, neurons do not occupy all the space; they only occupy less than 10% of the brain space.that is, more than 90% of the laser is wasted scanning parts of the brain that have no information, such as areas between neurons.therefore, if we can develop a "smart" laser light source (adaptive excitation source, AES) and synchronize the scanning of the light source with the microscope, so that when the microscope scans the valid information, the laser light source will be turned on; when the microscope scans the invalid information, the laser light source will be turned off (of course, the premise is that we need to scan the whole area first to know where the effective area is).in this way, Bo Li and Chris Xu again increased the number of recordable neurons by more than 30 times without damaging the brain! Figure 1 shows the working principle of the system.at present, their work has demonstrated an imaging depth of 750 μ m, a large FOV of 700x700 μ m, and an imaging speed of 30 frames per second, including both two-photon imaging and three-photon imaging. Figure 1: the working principle of adaptive light source AES. (a) the periodic light pulses are sent to a multiphoton laser scanning microscope to obtain neuron images. (b) when the neuron image is obtained, the information is sent back to AES. AES sends non periodic light pulses into the multi photon laser scanning microscope. Because the light source and microscope are synchronous, each light pulse is scanned on the neuron. although improving the recording of brain activity will make it possible for humans to further explore the brain, the idea that light sources can adapt to sample information represents a new direction of imaging systems. this technology will not only bring a breakthrough in brain research, but also bring reform to the whole imaging technology field. AES can be used in combination with any microscope, which can be applied to two-photon microscope and three-photon microscope, which makes the technology can be directly applied to the field of imaging. original link: plate maker: Ke