Core Viewpoint - A team of researchers from Peking University and Beijing Information Science and Technology University has developed a multi-color miniaturized two-photon microscope, enabling high-resolution imaging of the deep brain in freely moving mice, marking a significant advancement in brain science research [1][2]. Group 1: Technological Advancements - The new microscope allows for "color live broadcasting" of brain activity, significantly enhancing the understanding of neural circuits and the pathological mechanisms of brain diseases [1]. - The fourth-generation system achieves breakthroughs in multi-color excitation, deep brain imaging, and multi-scale observation, improving upon previous iterations that focused on single-color imaging and limited depth [1][2]. - The microscope's imaging depth exceeds 850 micrometers, three times deeper than previous miniaturized two-photon technologies, allowing for detailed observation of deeper brain structures [2]. Group 2: Research Applications - The technology enables the observation of complex interactions between different cell types using various fluorescent proteins, providing insights into cellular behavior in conditions like Alzheimer's disease [2]. - The microscope has already been successfully commercialized and exported to multiple countries, indicating its potential for widespread application in neuroscience research [3]. - Future research plans include integrating optogenetics to create a "read-write" loop for controlling specific neurons and increasing imaging speed to record brain activity in real-time [3].

Core Viewpoint - The development of a multi-color miniaturized two-photon microscope enables high-resolution imaging of deep brain structures in freely moving mice, significantly advancing brain science research and understanding of neurological diseases [2][3]. Group 1: Technological Advancements - The new microscope represents a significant technological breakthrough, allowing for multi-color imaging and the observation of various cell types simultaneously, overcoming previous limitations of single-color imaging [3][4]. - The fourth-generation system has achieved advancements in three dimensions: multi-color excitation, deep brain imaging, and multi-scale observation, enhancing the ability to study complex neural interactions [3][4]. - The ultra-broadband anti-resonant hollow-core fiber developed allows for low-loss, low-dispersion transmission of multi-wavelength femtosecond pulse lasers, which is crucial for observing multiple cellular functions [4]. Group 2: Research Implications - The microscope has been successfully used to visualize dynamic changes in brain cells and organelles in Alzheimer's disease model mice, providing critical insights into early cellular changes associated with the disease [4]. - The technology has been fully domesticated and has already been exported to multiple countries, indicating its potential for international application [4]. Group 3: Future Research Directions - Future research will focus on integrating optogenetics to create a "read-write" loop, enabling both the reading of neuronal electrical activity and the optical manipulation of specific neurons [5]. - There is a goal to increase imaging speed from 10-20 Hz to 1 kHz, allowing for real-time recording of brain electrical activity [5].