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High-speed, miniaturized fluorescence microscopy in freely moving mice

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Abstract

A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca2+ dynamics.

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Figure 1: Miniaturized fluorescence microscopy for high-speed brain imaging in freely behaving mice.
Figure 2: High-speed imaging of cerebral microcirculation in freely behaving mice.
Figure 3: High-speed imaging of cerebellar Purkinje cell dendritic Ca2+ spiking.
Figure 4: Comparisons of Purkinje cell Ca2+ spiking during rest and motor behavior.

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Acknowledgements

Our work was supported by grants to M.J.S. from the US National Science Foundation (NSF), the Office of Naval Research, the Packard and Beckman Foundations, and the NSF Center for Biophotonics, and by research fellowships from the NSF (B.A.F., E.A.M. and L.D.B.), Stanford University (L.D.B.), the International Human Frontier Science Program Organization (A.N.) and the Stanford University–US National Institutes of Health Biotechnology (E.D.C.) and Biophysics (R.P.J.B.) training grants. We thank Stanford University's Varian Machine Shop, D. Profitt and A. Lui for technical assistance.

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Correspondence to Mark J Schnitzer.

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Flusberg, B., Nimmerjahn, A., Cocker, E. et al. High-speed, miniaturized fluorescence microscopy in freely moving mice. Nat Methods 5, 935–938 (2008). https://doi.org/10.1038/nmeth.1256

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