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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnmeth.1256/MediaObjects/41592_2008_Article_BFnmeth1256_Fig1_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnmeth.1256/MediaObjects/41592_2008_Article_BFnmeth1256_Fig2_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnmeth.1256/MediaObjects/41592_2008_Article_BFnmeth1256_Fig3_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fnmeth.1256/MediaObjects/41592_2008_Article_BFnmeth1256_Fig4_HTML.jpg)
Similar content being viewed by others
References
Ferezou, I., Bolea, S. & Petersen, C.C. Neuron 50, 617–629 (2006).
Yamaguchi, S. et al. Nature 409, 684 (2001).
Adelsberger, H., Garaschuk, O. & Konnerth, A. Nat. Neurosci. 8, 988–990 (2005).
Murayama, M., Perez-Garci, E., Luscher, H.R. & Larkum, M.E. J. Neurophysiol. 98, 1791–1805 (2007).
Poe, G.R., Kristensen, M.P., Rector, D.M. & Harper, R.M. Neuroscience 72, 39–48 (1996).
Helmchen, F., Fee, M.S., Tank, D.W. & Denk, W. Neuron 31, 903–912 (2001).
Dombeck, D.A., Khabbaz, A.N., Collman, F., Adelman, T.L. & Tank, D.W. Neuron 56, 43–57 (2007).
Flusberg, B.A. et al. Nat. Methods 2, 941–950 (2005).
Jung, J.C., Mehta, A.D., Aksay, E., Stepnoski, R. & Schnitzer, M.J. J. Neurophysiol. 92, 3121–3133 (2004).
Schaffer, C.B. et al. PLoS Biol. 4, e22 (2006).
Gobel, W. & Helmchen, F. J. Neurophysiol. 98, 3770–3779 (2007).
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).
Schiffmann, S.N. et al. Proc. Natl. Acad. Sci. USA 96, 5257–5262 (1999).
Harris, K.D., Henze, D.A., Csicsvari, J., Hirase, H. & Buzsaki, G. J. Neurophysiol. 84, 401–414 (2000).
Andersson, G. & Armstrong, D.M. J. Physiol. (Lond.) 385, 107–134 (1987).
Welsh, J.P., Lang, E.J., Suglhara, I. & Llinas, R. Nature 374, 453–457 (1995).
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.
Author information
Authors and Affiliations
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–2, Supplementary Methods (PDF 1517 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nmeth.1256
This article is cited by
-
Cerebellar Purkinje cells combine sensory and motor information to predict the sensory consequences of active self-motion in macaques
Nature Communications (2024)
-
Unsupervised full-color cellular image reconstruction through disordered optical fiber
Light: Science & Applications (2023)
-
Multiplex translaminar imaging in the spinal cord of behaving mice
Nature Communications (2023)
-
Fully Integrated Ultra-thin Intraoperative Micro-imager for Cancer Detection Using Upconverting Nanoparticles
Molecular Imaging and Biology (2023)
-
Deep-learning two-photon fiberscopy for video-rate brain imaging in freely-behaving mice
Nature Communications (2022)