Miniature Fluorescence Microscopy for Imaging Brain Activity in Freely-Behaving Animals
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REVIEW
Miniature Fluorescence Microscopy for Imaging Brain Activity in Freely-Behaving Animals Shiyuan Chen1 • Zichen Wang1 • Dong Zhang2 • Aiming Wang3,4 • Liangyi Chen1 Heping Cheng1 • Runlong Wu1
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Received: 18 March 2020 / Accepted: 11 May 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
Abstract An ultimate goal of neuroscience is to decipher the principles underlying neuronal information processing at the molecular, cellular, circuit, and system levels. The advent of miniature fluorescence microscopy has furthered the quest by visualizing brain activities and structural dynamics in animals engaged in self-determined behaviors. In this brief review, we summarize recent advances in miniature fluorescence microscopy for neuroscience, focusing mostly on two mainstream solutions – miniature single-photon microscopy, and miniature two-photon microscopy. We discuss their technical advantages and limitations as well as unmet challenges for future improvement. Examples of preliminary applications are also presented to reflect on a new trend of brain imaging in experimental paradigms involving body movements, long and complex protocols, and even disease progression and aging. Keywords Miniature fluorescence microscopy Brain imaging Two-photon microscopy Neuronal information processing & Runlong Wu [email protected] 1
State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, PKU-Nanjing Institute of Translational Medicine, Peking University, Beijing 100871, China
2
Academy of Advanced Interdisciplinary Study, Peking University, Beijing 100871, China
3
Department of Electronics, Peking University, Beijing 100871, China
4
State Key Laboratory of Advanced Optical Communication System and Networks, Peking University, Beijing 100871, China
Introduction The past few decades have witnessed great expansion and transformation of the neurosciences into the dawning of a new era of brain science. To decipher the principles underlying neuronal information processing at the molecular, cellular, circuit, and system levels, it is imperative to characterize the structural organization and functional dynamics of the brain at different spatial scales. Macroscopic brain imaging modalities include magnetic resonance imaging, positron emission tomography, X-ray computed tomography, and the more recently-invented photoacoustic tomography. For ultrastructural studies, microscopic brain imaging modalities include electron microscopy and different types of super-resolution optical microscopy. However, to bridge animal behaviors with the activity of spines, neurons, and neuronal circuits in specific brain regions, optical imaging technology is the ideal choice because it enables both high spatiotemporal resolution and cell-type specificity in vivo. However, traditional benchtop optical microscopes are bulky and rigid, and require the animals to be anesthetized or head-fixed while imaging [1–3]. The physical constraints an
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