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Advanced Miniature Microscopy for Brain Imaging

  • Weijian Zong
  • Liangyi Chen
Chapter
Part of the Progress in Optical Science and Photonics book series (POSP, volume 5)

Abstract

To image neuronal activities down to single spines in freely behaving animal has already been the holy grail of neuroscientists. To achieve that goal, two-photon microscope must be miniaturized to be attached to the animal without interfering animal movements. In the past fifteen years, many groups have published different designs, albeit that none of them is not widely used by the neuroscience community. Here, we have summarized the major challenges that prevent prevalent applications of current miniature two-photon microscopy (TPM) for high-resolution imaging in freely behaving mice, and different configurations that may be used to address each challenge. Based on this theoretical analysis, we have provided detailed design of our high-resolution, miniaturized two-photon microscope (FHIRM-TPM) and its latest revisions that enable volumetric imaging capability and larger field of view and deeper penetration depth.

Keywords

Two-photon microscopy Neural function Miniature microscope 

References

  1. 1.
    M. Minderer, C.D. Harvey, F. Donato, E.I. Moser, Neuroscience: virtual reality explored. Nature 533(7603), 324–325 (2016).  https://doi.org/10.1038/nature17899CrossRefGoogle Scholar
  2. 2.
    Z.M. Aghajan, L. Acharya, J.J. Moore, J.D. Cushman, C. Vuong, M.R. Mehta, Impaired spatial selectivity and intact phase precession in two-dimensional virtual reality. Nat. Neurosci. 18(1), 121–128 (2015).  https://doi.org/10.1038/nn.3884CrossRefGoogle Scholar
  3. 3.
    E.J. Hamel, B.F. Grewe, J.G. Parker, M.J. Schnitzer, Cellular level brain imaging in behaving mammals: an engineering approach. Neuron 86(1), 140–159 (2015).  https://doi.org/10.1016/j.neuron.2015.03.055CrossRefGoogle Scholar
  4. 4.
    C.K. Kim, S.J. Yang, N. Pichamoorthy, N.P. Young, I. Kauvar, J.H. Jennings, T.N. Lerner, A. Berndt, S.Y. Lee, C. Ramakrishnan, T.J. Davidson, M. Inoue, H. Bito, K. Deisseroth, Simultaneous fast measurement of circuit dynamics at multiple sites across the mammalian brain. Nat. Methods 13(4), 325–328 (2016).  https://doi.org/10.1038/nmeth.3770CrossRefGoogle Scholar
  5. 5.
    I. Ferezou, S. Bolea, C.C. Petersen, Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice. Neuron 50(4), 617–629 (2006).  https://doi.org/10.1016/j.neuron.2006.03.043CrossRefGoogle Scholar
  6. 6.
    K.K. Ghosh, L.D. Burns, E.D. Cocker, A. Nimmerjahn, Y. Ziv, A.E. Gamal, M.J. Schnitzer, Miniaturized integration of a fluorescence microscope. Nat. Methods 8(10), 871–878 (2011).  https://doi.org/10.1038/nmeth.1694CrossRefGoogle Scholar
  7. 7.
    Z. Gorocs, Y. Rivenson, H. Ceylan Koydemir, D. Tseng, T.L. Troy, V. Demas, A. Ozcan, Quantitative fluorescence sensing through highly autofluorescent, scattering, and absorbing media using mobile microscopy. ACS Nano 10(9), 8989–8999 (2016).  https://doi.org/10.1021/acsnano.6b05129CrossRefGoogle Scholar
  8. 8.
    F. Helmchen, M.S. Fee, D.W. Tank, W. Denk, A miniature head-mounted two-photon microscope. Neuron 31(6), 903–912 (2001).  https://doi.org/10.1016/s0896-6273(01)00421-4CrossRefGoogle Scholar
  9. 9.
    C.J. Engelbrecht, R.S. Johnston, E.J. Seibel, F. Helmchen, Ultra-compact fiber-optic two-photon microscope for functional fluorescence imaging in vivo. Opt. Express 16(8), 5556 (2008).  https://doi.org/10.1364/oe.16.005556CrossRefGoogle Scholar
  10. 10.
    W. Piyawattanametha, E.D. Cocker, L.D. Burns, R.P.J. Barretto, J.C. Jung, H. Ra, O. Solgaard, M.J. Schnitzer, In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror. Opt. Lett. 34(15), 2309 (2009).  https://doi.org/10.1364/ol.34.002309CrossRefGoogle Scholar
  11. 11.
    J. Sawinski, D.J. Wallace, D.S. Greenberg, S. Grossmann, W. Denk, J.N.D. Kerr, Visually evoked activity in cortical cells imaged in freely moving animals. Proc. Natl. Acad. Sci. 106(46), 19557–19562 (2009).  https://doi.org/10.1073/pnas.0903680106CrossRefGoogle Scholar
  12. 12.
    W. Zong, R. Wu, M. Li, Y. Hu, Y. Li, J. Li, H. Rong, H. Wu, Y. Xu, Y. Lu, H. Jia, M. Fan, Z. Zhou, Y. Zhang, A. Wang, L. Chen, H. Cheng, Fast high-resolution miniature two-photon microscopy for brain imaging in freely behaving mice. Nat. Methods 14(7), 713–719 (2017).  https://doi.org/10.1038/nmeth.4305CrossRefGoogle Scholar
  13. 13.
    D.R. Rivera, C.M. Brown, D.G. Ouzounov, I. Pavlova, D. Kobat, W.W. Webb, C. Xu, Compact and flexible raster scanning multiphoton endoscope capable of imaging unstained tissue. Proc. Natl. Acad. Sci. U. S. A. 108(43), 17598–17603 (2011).  https://doi.org/10.1073/pnas.1114746108CrossRefGoogle Scholar
  14. 14.
    Y. Zhang, M.L. Akins, K. Murari, J. Xi, M.J. Li, K. Luby-Phelps, M. Mahendroo, X. Li, A compact fiber-optic SHG scanning endomicroscope and its application to visualize cervical remodeling during pregnancy. Proc. Natl. Acad. Sci. U. S. A. 109(32), 12878–12883 (2012).  https://doi.org/10.1073/pnas.1121495109CrossRefGoogle Scholar
  15. 15.
    F. Helmchen, D.W. Tank, W. Denk, Enhanced two-photon excitation through optical fiber by single-mode propagation in a large core. Appl. Opt. 41(15), 2930 (2002).  https://doi.org/10.1364/ao.41.002930CrossRefGoogle Scholar
  16. 16.
    G.P. Agrawal, Applications of nonlinear fiber optics. Optics and Photonics (2001)Google Scholar
  17. 17.
    W. Gobel, A. Nimmerjahn, F. Helmchen, Distortion-free delivery of nanojoule femtosecond pulses from a Ti:sapphire laser through a hollow-core photonic crystal fiber. Opt. Lett. 29(11), 1285–1287 (2004)CrossRefGoogle Scholar
  18. 18.
    C. Wang, N. Ji, Characterization and improvement of three-dimensional imaging performance of GRIN-lens-based two-photon fluorescence endomicroscopes with adaptive optics. Opt. Express 21(22), 27142–27154 (2013).  https://doi.org/10.1364/OE.21.027142CrossRefGoogle Scholar
  19. 19.
    Sawinski Jr, W. Denk, Miniature random-access fiber scanner for in vivo multiphoton imaging. J. Appl. Phys. 102(3), 034701 (2007).  https://doi.org/10.1063/1.2763945CrossRefGoogle Scholar
  20. 20.
    M.T. Myaing, D.J. MacDonald, X. Li, Fiber-optic scanning two-photon fluorescence endoscope. Opt. Lett. 31(8), 1076 (2006).  https://doi.org/10.1364/ol.31.001076CrossRefGoogle Scholar
  21. 21.
    W. Piyawattanametha, R.P.J. Barretto, T.H. Ko, B.A. Flusberg, E.D. Cocker, H. Ra, D. Lee, O. Solgaard, M.J. Schnitzer, Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror. Opt. Lett. 31(13), 2018 (2006).  https://doi.org/10.1364/ol.31.002018CrossRefGoogle Scholar
  22. 22.
    W. Jung, S. Tang, D.T. McCormic, T. Xie, Y.-C. Ahn, J. Su, I.V. Tomov, T.B. Krasieva, B.J. Tromberg, Z. Chen, Miniaturized probe based on a microelectromechanical system mirror for multiphoton microscopy. Opt. Lett. 33(12), 1324 (2008).  https://doi.org/10.1364/ol.33.001324CrossRefGoogle Scholar
  23. 23.
    A. Grayson, A BioMEMS review: MEMS technology for physiologically integrated devices. Proc. IEEE 92(1), 6–21 (2004)CrossRefGoogle Scholar
  24. 24.
    V. Milanovic, Gimbal-less monolithic silicon actuators for tip–tilt–piston micromirror applications. J. Sel. Topics Quantum Electron. 10(3), 462–471 (2004)CrossRefGoogle Scholar
  25. 25.
    R. Prakash, O. Yizhar, B. Grewe, C. Ramakrishnan, N. Wang, I. Goshen, A.M. Packer, D.S. Peterka, R. Yuste, M.J. Schnitzer, K. Deisseroth, Two-photon optogenetic toolbox for fast inhibition, excitation and bistable modulation. Nat. Methods 9(12), 1171–1179 (2012).  https://doi.org/10.1038/nmeth.2215CrossRefGoogle Scholar
  26. 26.
    J.P. Rickgauer, K. Deisseroth, D.W. Tank, Simultaneous cellular-resolution optical perturbation and imaging of place cell firing fields. Nat. Neurosci. 17(12), 1816–1824 (2014).  https://doi.org/10.1038/nn.3866CrossRefGoogle Scholar
  27. 27.
    G. Matz, B. Messerschmidt, H. Gross, Design and evaluation of new color-corrected rigid endomicroscopic high NA GRIN-objectives with a sub-micron resolution and large field of view. Opt. Express 24(10), 10987–11001 (2016).  https://doi.org/10.1364/OE.24.010987CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular MedicinePeking UniversityBeijingChina

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