The analysis of brain connectivity maps and functional dynamics maps necessitates the development of wearable microscopic imaging tools for freely moving animals. Currently, miniaturized single-photon and two-photon microscopes can only see the superficial layers of the cerebral cortex and cannot penetrate through the entire cortex to achieve non-invasive imaging of deeper brain regions. The hippocampus, located beneath the cerebral cortex and corpus callosum, plays a crucial role in memory consolidation, spatial navigation, and emotional processing. Due to the highly scattered optical properties of brain tissue, particularly in the corpus callosum, neuroscientists have long faced a formidable challenge in overcoming limitations related to imaging depth and achieving non-invasive imaging of deep brain regions such as the hippocampus.
Chunzhu Zhao, a research assistant professor at Peking University, specializes in deep brain imaging and has proposed an optical configuration that maximizes the collection efficiency of scattering fluorescence. Together with his team, he successfully developed a miniaturized three-photon microscope weighing 2.17g for deep brain imaging. This breakthrough surpasses the previous microscopes’ limitations on imaging depth and enables functional imaging of the entire cerebral cortex and hippocampal neurons in freely behaving mice for the first time. It provides a novel observational tool to uncover the mechanisms underlying neural functional connections within deep brain structures and introduces a new research paradigm.
Zhao also successfully developed the first miniature two-photon microscope with a millimeter field of view, significantly expanding the maximum three-dimensional imaging volume by 6.6 times compared to its predecessors. This advancement empowers neuroscientists in deciphering neuronal population dynamics in experimental paradigms allowing for animal’s free movement.
Biomedical imaging necessitates interdisciplinary integration for the development of state-of-the-art instruments. Zhao possesses a strong foundation in optics and extensive experience in the intricate instrument design. As an exceptional innovative talent in the field of biomedical imaging, his accomplishments are truly remarkable. Moving forward, he will continue to advance novel imaging instruments, surpassing the boundaries of deep brain imaging and forging cutting-edge tools for revolutionary fundamental research in brain science.
