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High-speed, miniaturized fluorescence microscopy in freely moving mice

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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References

  1. Ferezou, I., Bolea, S. & Petersen, C.C. Neuron 50, 617–629 (2006).

    Article  CAS  Google Scholar 

  2. Yamaguchi, S. et al. Nature 409, 684 (2001).

    Article  CAS  Google Scholar 

  3. Adelsberger, H., Garaschuk, O. & Konnerth, A. Nat. Neurosci. 8, 988–990 (2005).

    Article  CAS  Google Scholar 

  4. Murayama, M., Perez-Garci, E., Luscher, H.R. & Larkum, M.E. J. Neurophysiol. 98, 1791–1805 (2007).

    Article  Google Scholar 

  5. Poe, G.R., Kristensen, M.P., Rector, D.M. & Harper, R.M. Neuroscience 72, 39–48 (1996).

    Article  CAS  Google Scholar 

  6. Helmchen, F., Fee, M.S., Tank, D.W. & Denk, W. Neuron 31, 903–912 (2001).

    Article  CAS  Google Scholar 

  7. Dombeck, D.A., Khabbaz, A.N., Collman, F., Adelman, T.L. & Tank, D.W. Neuron 56, 43–57 (2007).

    Article  CAS  Google Scholar 

  8. Flusberg, B.A. et al. Nat. Methods 2, 941–950 (2005).

    Article  CAS  Google Scholar 

  9. Jung, J.C., Mehta, A.D., Aksay, E., Stepnoski, R. & Schnitzer, M.J. J. Neurophysiol. 92, 3121–3133 (2004).

    Article  Google Scholar 

  10. Schaffer, C.B. et al. PLoS Biol. 4, e22 (2006).

    Article  Google Scholar 

  11. Gobel, W. & Helmchen, F. J. Neurophysiol. 98, 3770–3779 (2007).

    Article  Google Scholar 

  12. Llinas, R.R., Walton, K.D. & Lang, E.J. in The Synaptic Organization of the Brain. (ed., G. Shepherd), 271–310 (Oxford University Press, Oxford, 2004).

    Book  Google Scholar 

  13. Schiffmann, S.N. et al. Proc. Natl. Acad. Sci. USA 96, 5257–5262 (1999).

    Article  CAS  Google Scholar 

  14. Harris, K.D., Henze, D.A., Csicsvari, J., Hirase, H. & Buzsaki, G. J. Neurophysiol. 84, 401–414 (2000).

    Article  CAS  Google Scholar 

  15. Andersson, G. & Armstrong, D.M. J. Physiol. (Lond.) 385, 107–134 (1987).

    Article  CAS  Google Scholar 

  16. Welsh, J.P., Lang, E.J., Suglhara, I. & Llinas, R. Nature 374, 453–457 (1995).

    Article  CAS  Google Scholar 

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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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