Abstract

Fluorescence microendoscopy is becoming a promising approach for deep brain imaging, but the current technology for visualizing neurons on a single focal plane limits the experimental efficiency and the pursuit of three-dimensional functional neural circuit architectures. Here we present a novel fast varifocal two-photon microendoscope system equipped with a gradient refractive index (GRIN) lens and an electrically tunable lens (ETL). This microendoscope enables quasi-simultaneous imaging of the neuronal network activity of deep brain areas at multiple focal planes separated by 85–120 µm at a fast scan rate of 7.5–15 frames per second per plane, as demonstrated in calcium imaging of the mouse dorsal CA1 hippocampus and amygdala in vivo.

© 2017 Optical Society of America

Full Article  |  PDF Article
OSA Recommended Articles
Adaptive optical versus spherical aberration corrections for in vivo brain imaging

Raphaël Turcotte, Yajie Liang, and Na Ji
Biomed. Opt. Express 8(8) 3891-3902 (2017)

Multiphoton in vivo imaging with a femtosecond semiconductor disk laser

Fabian F. Voigt, Florian Emaury, Philipp Bethge, Dominik Waldburger, Sandro M. Link, Stefano Carta, Alexander van der Bourg, Fritjof Helmchen, and Ursula Keller
Biomed. Opt. Express 8(7) 3213-3231 (2017)

Plastic embedding immunolabeled large-volume samples for three-dimensional high-resolution imaging

Yadong Gang, Xiuli Liu, Xiaojun Wang, Qi Zhang, Hongfu Zhou, Ruixi Chen, Ling Liu, Yao Jia, Fangfang Yin, Gong Rao, Jiadong Chen, and Shaoqun Zeng
Biomed. Opt. Express 8(8) 3583-3596 (2017)

References

  • View by:
  • |
  • |
  • |

  1. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
    [Crossref] [PubMed]
  2. W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).
    [Crossref] [PubMed]
  3. A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
    [Crossref] [PubMed]
  4. D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
    [Crossref] [PubMed]
  5. M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
    [Crossref] [PubMed]
  6. M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
    [Crossref] [PubMed]
  7. R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
    [Crossref] [PubMed]
  8. N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
    [Crossref] [PubMed]
  9. D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
    [Crossref] [PubMed]
  10. M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
    [Crossref] [PubMed]
  11. J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
    [Crossref] [PubMed]
  12. R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
    [Crossref] [PubMed]
  13. M. E. Bocarsly, W. C. Jiang, C. Wang, J. T. Dudman, N. Ji, and Y. Aponte, “Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain,” Biomed. Opt. Express 6(11), 4546–4556 (2015).
    [Crossref] [PubMed]
  14. A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
    [Crossref] [PubMed]
  15. K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
    [Crossref] [PubMed]
  16. B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
    [Crossref] [PubMed]
  17. S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
    [Crossref] [PubMed]
  18. B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
    [Crossref] [PubMed]
  19. M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
    [Crossref] [PubMed]
  20. A. T. Popescu and D. Paré, “Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells,” J. Neurophysiol. 105(2), 687–696 (2011).
    [Crossref] [PubMed]
  21. S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
    [Crossref] [PubMed]
  22. O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
    [Crossref] [PubMed]

2017 (2)

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

2016 (1)

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

2015 (5)

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

M. E. Bocarsly, W. C. Jiang, C. Wang, J. T. Dudman, N. Ji, and Y. Aponte, “Minimally invasive microendoscopy system for in vivo functional imaging of deep nuclei in the mouse brain,” Biomed. Opt. Express 6(11), 4546–4556 (2015).
[Crossref] [PubMed]

2013 (2)

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

2012 (2)

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

2011 (3)

A. T. Popescu and D. Paré, “Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells,” J. Neurophysiol. 105(2), 687–696 (2011).
[Crossref] [PubMed]

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
[Crossref] [PubMed]

2010 (1)

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

2009 (1)

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
[Crossref] [PubMed]

2004 (3)

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

1997 (1)

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).
[Crossref] [PubMed]

1990 (1)

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Aksay, E.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Aponte, Y.

Barretto, R. P. J.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
[Crossref] [PubMed]

Bocarsly, M. E.

Burns, L. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Cheng, Y. T.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Clark, C. G.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Cocker, E. D.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Crowley, J. C.

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

Cruz-Hernández, J. C.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Daftary, S.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Denk, W.

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).
[Crossref] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Dombeck, D. A.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Dudman, J. T.

Ehrlich, D. E.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Feng, D. D.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Funabiki, K.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Gamal, A. E.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Gengyo-Ando, K.

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Ghosh, K. K.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Goto, A.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Grenier, F.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Grewe, B. F.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

B. F. Grewe, F. F. Voigt, M. van ’t Hoff, and F. Helmchen, “Fast two-layer two-photon imaging of neuronal cell populations using an electrically tunable lens,” Biomed. Opt. Express 2(7), 2035–2046 (2011).
[Crossref] [PubMed]

Gründemann, J.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Harvey, C. D.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Hayashi, Y.

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Helmchen, F.

Hibi, T.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Homma, C.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Horton, N. G.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Ikegaya, Y.

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Inutsuka, A.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Jasnow, A. M.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Jercog, P. E.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Ji, N.

Jiang, W. C.

Jung, J. C.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Kagawa-Nagamura, Y.

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Kamioka, Y.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Kasischke, K. A.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Katz, L. C.

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

Kawakami, R.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Kawano, M.

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

Kawasaki, H.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Kitch, L. J.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Kobat, D.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Kobayashi, C.

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Kozawa, Y.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Larkin, M. C.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Larkum, M. E.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Lecoq, J. A.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Levene, M. J.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Li, J. Z.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Looger, L. L.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Lüthi, A.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Madsen, T. E.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Manita, S.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Marshall, J. D.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Masamizu, Y.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Matsubara, C.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Matsuda, M.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Matsumoto, T.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Matsuzaki, M.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Mehta, A. D.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Messerschmidt, B.

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
[Crossref] [PubMed]

Mizrahi, A.

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

Mizukami, H.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Molloy, R. P.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

Murayama, M.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Nakahara, I.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Nakai, J.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Nakanishi, S.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Nemoto, T.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Nimmerjahn, A.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Nishimura, N.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Odagawa, M.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Ohkura, M.

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Ohtsuka, M.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Ota, K.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Ouzounov, D. G.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Ozawa, K.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Paré, D.

A. T. Popescu and D. Paré, “Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells,” J. Neurophysiol. 105(2), 687–696 (2011).
[Crossref] [PubMed]

Parker, J. G.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Popescu, A. T.

A. T. Popescu and D. Paré, “Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells,” J. Neurophysiol. 105(2), 687–696 (2011).
[Crossref] [PubMed]

Rainnie, D. G.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Reimer, J.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Ryan, S. J.

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Sadakane, O.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Sadakari, J.

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Sasaki, T.

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

Sato, A.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Sato, M.

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Sato, S.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Sawada, K.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Schaffer, C. B.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Schnitzer, M. J.

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
[Crossref] [PubMed]

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Shtoyerman, E.

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

Stepnoski, R.

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

Strickler, J. H.

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Sumiyama, K.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Suzuki, T.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Svoboda, K.

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).
[Crossref] [PubMed]

Takaji, M.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Tank, D. W.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Terada, S.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Tian, L.

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Tolias, A. S.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

van ’t Hoff, M.

Voigt, F. F.

Wang, C.

Wang, K.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Wang, M.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Wang, T.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

Watakabe, A.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Webb, W. W.

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Wise, F. W.

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Xu, C.

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Yamada, K.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Yamaguchi, T.

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Yamamori, T.

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

Yamanaka, A.

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Yanagawa, Y.

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

Yokoyama, H.

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Ziv, Y.

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Cell Reports (1)

O. Sadakane, Y. Masamizu, A. Watakabe, S. Terada, M. Ohtsuka, M. Takaji, H. Mizukami, K. Ozawa, H. Kawasaki, M. Matsuzaki, and T. Yamamori, “Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates,” Cell Reports 13(9), 1989–1999 (2015).
[Crossref] [PubMed]

J. Neurophysiol. (3)

A. T. Popescu and D. Paré, “Synaptic interactions underlying synchronized inhibition in the basal amygdala: evidence for existence of two types of projection cells,” J. Neurophysiol. 105(2), 687–696 (2011).
[Crossref] [PubMed]

M. J. Levene, D. A. Dombeck, K. A. Kasischke, R. P. Molloy, and W. W. Webb, “In vivo multiphoton microscopy of deep brain tissue,” J. Neurophysiol. 91(4), 1908–1912 (2004).
[Crossref] [PubMed]

J. C. Jung, A. D. Mehta, E. Aksay, R. Stepnoski, and M. J. Schnitzer, “In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy,” J. Neurophysiol. 92(5), 3121–3133 (2004).
[Crossref] [PubMed]

J. Neurosci. (1)

A. Mizrahi, J. C. Crowley, E. Shtoyerman, and L. C. Katz, “High-resolution in vivo imaging of hippocampal dendrites and spines,” J. Neurosci. 24(13), 3147–3151 (2004).
[Crossref] [PubMed]

Nat. Methods (3)

D. G. Ouzounov, T. Wang, M. Wang, D. D. Feng, N. G. Horton, J. C. Cruz-Hernández, Y. T. Cheng, J. Reimer, A. S. Tolias, N. Nishimura, and C. Xu, “In vivo three-photon imaging of activity of GCaMP6-labeled neurons deep in intact mouse brain,” Nat. Methods 14(4), 388–390 (2017).
[Crossref] [PubMed]

R. P. J. Barretto, B. Messerschmidt, and M. J. Schnitzer, “In vivo fluorescence imaging with high-resolution microlenses,” Nat. Methods 6(7), 511–512 (2009).
[Crossref] [PubMed]

K. K. Ghosh, L. D. Burns, E. D. Cocker, A. Nimmerjahn, Y. Ziv, A. E. Gamal, and M. J. Schnitzer, “Miniaturized integration of a fluorescence microscope,” Nat. Methods 8(10), 871–878 (2011).
[Crossref] [PubMed]

Nat. Neurosci. (1)

D. A. Dombeck, C. D. Harvey, L. Tian, L. L. Looger, and D. W. Tank, “Functional imaging of hippocampal place cells at cellular resolution during virtual navigation,” Nat. Neurosci. 13(11), 1433–1440 (2010).
[Crossref] [PubMed]

Nat. Photonics (1)

N. G. Horton, K. Wang, D. Kobat, C. G. Clark, F. W. Wise, C. B. Schaffer, and C. Xu, “In vivo three-photon microscopy of subcortical structures within an intact mouse brain,” Nat. Photonics 7(3), 205–209 (2013).
[Crossref] [PubMed]

Nature (1)

B. F. Grewe, J. Gründemann, L. J. Kitch, J. A. Lecoq, J. G. Parker, J. D. Marshall, M. C. Larkin, P. E. Jercog, F. Grenier, J. Z. Li, A. Lüthi, and M. J. Schnitzer, “Neural ensemble dynamics underlying a long-term associative memory,” Nature 543(7647), 670–675 (2017).
[Crossref] [PubMed]

Neurobiol. Learn. Mem. (1)

M. Sato, M. Kawano, Y. Yanagawa, and Y. Hayashi, “In vivo two-photon imaging of striatal neuronal circuits in mice,” Neurobiol. Learn. Mem. 135, 146–151 (2016).
[Crossref] [PubMed]

Neuron (2)

W. Denk and K. Svoboda, “Photon upmanship: why multiphoton imaging is more than a gimmick,” Neuron 18(3), 351–357 (1997).
[Crossref] [PubMed]

S. Manita, T. Suzuki, C. Homma, T. Matsumoto, M. Odagawa, K. Yamada, K. Ota, C. Matsubara, A. Inutsuka, M. Sato, M. Ohkura, A. Yamanaka, Y. Yanagawa, J. Nakai, Y. Hayashi, M. E. Larkum, and M. Murayama, “A top-down cortical circuit for accurate sensory perception,” Neuron 86(5), 1304–1316 (2015).
[Crossref] [PubMed]

PLoS One (3)

M. Ohkura, T. Sasaki, J. Sadakari, K. Gengyo-Ando, Y. Kagawa-Nagamura, C. Kobayashi, Y. Ikegaya, and J. Nakai, “Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals,” PLoS One 7(12), e51286 (2012).
[Crossref] [PubMed]

M. Sato, M. Kawano, M. Ohkura, K. Gengyo-Ando, J. Nakai, and Y. Hayashi, “Generation and imaging of transgenic mice that express G-CaMP7 under a tetracycline response element,” PLoS One 10(5), e0125354 (2015).
[Crossref] [PubMed]

S. J. Ryan, D. E. Ehrlich, A. M. Jasnow, S. Daftary, T. E. Madsen, and D. G. Rainnie, “Spike-timing precision and neuronal synchrony are enhanced by an interaction between synaptic inhibition and membrane oscillations in the amygdala,” PLoS One 7(4), e35320 (2012).
[Crossref] [PubMed]

Proc. Natl. Acad. Sci. U.S.A. (1)

A. Goto, I. Nakahara, T. Yamaguchi, Y. Kamioka, K. Sumiyama, M. Matsuda, S. Nakanishi, and K. Funabiki, “Circuit-dependent striatal PKA and ERK signaling underlies rapid behavioral shift in mating reaction of male mice,” Proc. Natl. Acad. Sci. U.S.A. 112(21), 6718–6723 (2015).
[Crossref] [PubMed]

Sci. Rep. (1)

R. Kawakami, K. Sawada, A. Sato, T. Hibi, Y. Kozawa, S. Sato, H. Yokoyama, and T. Nemoto, “Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser,” Sci. Rep. 3(1), 1014 (2013).
[Crossref] [PubMed]

Science (1)

W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
[Crossref] [PubMed]

Supplementary Material (4)

NameDescription
» Visualization 1       Dorsal hippocampal CA1 area of the transgenic mouse imaged using the microendoscope. Overlaid images of G-CaMP7 (green) and DsRed2 (red) fluorescence signals are shown. Depths are indicated in the upper left corner of the movie.
» Visualization 2       Spontaneous activity of hippocampal CA1 circuits imaged using the microendoscope. The images corresponding to the first minute are shown in this movie. The playback speed is 5x faster than the speed of real activity.
» Visualization 3       Depth-specific cellular activity in the dorsal CA1 hippocampus imaged using the fast varifocal microendoscope. Images acquired quasi-simultaneously at different depths are shown in top (0 V) and bottom (0.25 V, 85 µm below) panels.
» Visualization 4       Synchronous network activity in the amygdala imaged using the fast varifocal microendoscope. Images acquired quasi-simultaneously at different depths are shown in top (0 V) and bottom (0.35 V, 120 µm below) panels.

Cited By

OSA participates in Crossref's Cited-By Linking service. Citing articles from OSA journals and other participating publishers are listed here.

Alert me when this article is cited.


Figures (6)

Fig. 1
Fig. 1

Fast varifocal two-photon microendoscope. (a) Microendoscope setup. (b) A GRIN lens (left) and a stainless-steel guide cannula (right; 1 small division = 1 mm). (c) A mouse implanted with a guide cannula and a head plate.

Fig. 2
Fig. 2

Spatial resolutions of the two-photon microendoscope. Point spread functions obtained by imaging of fluorescent microspheres of 0.17 µm diameter with the GRIN lens (w/ GRIN) demonstrate the (a) lateral and (b) axial resolutions of the full two-photon microendoscope system, whereas those obtained without the GRIN lens (w/o GRIN) demonstrate resolutions of the two-photon microscope alone (c, d).

Fig. 3
Fig. 3

Relationship between control voltage and the focal shift. (a) Changes in the focal depth of the objective by an ETL can elicit focal shifts of the GRIN lens. (b) Relationship between control voltages to the current driver and its current output to the ETL. (c) Relationship between control voltages to the current driver and the focal shift. (d) Comparisons of images acquired at different focal depths using the ETL (ETL, upper panels) and those acquired at the corresponding depths using the z stepper motor (z step, lower panels). (e) The FWHMs of the PSFs of the x (left) and z (right) axes across the whole tuning range of the ETL.

Fig. 4
Fig. 4

Fast and reproducible focal shifts of the varifocal microendoscope. (a) Schematic representation of the image acquisition. Rectangular control voltage pulses of 1 V were delivered to shift the focal depth 340 µm during acquisition of every other frame. (b) Reference images of fluorescent microspheres were acquired by using the z stepper motor at depths of 0 µm (left column) and 340 µm below (right column). The areas enclosed by red boxes are magnified in the bottom to show depth-specific patterns of microsphere arrangements. (c) Example images of fast varifocal imaging. Two-dimensional correlation coefficients calculated using the first (REF1) and second (REF2) leftmost images as reference are shown in the top (vs. REF1) and bottom (vs. REF2) row, respectively, of the table. (d) Stability of fast varifocal imaging evaluated in 10-min imaging sessions with 0 V (−ETL) or 1 V (+ETL) voltage pulses applied during acquisition of every other frame. Note that the correlations between the reference frames (i.e., r = 1.0) at the origin of the x axis are not plotted for clarity.

Fig. 5
Fig. 5

Spontaneous activity of mouse hippocampal CA1 neuronal circuits imaged using fast varifocal two-photon microendoscope. (a) A coronal brain section of a Thy1-G-CaMP7-DsRed2 transgenic mouse that was implanted with a guide cannula for hippocampal imaging (HP: hippocampus; scale bar = 1 mm). (b) Dorsal hippocampal CA1 area of the transgenic mouse was imaged using the microendoscope at the surface (left, 0 µm) and 140 µm below (right, 140 µm). The red dotted box delineates the area imaged in (c) and (d) (A: anterior; L: lateral; scale bar = 200 µm). (c) G-CaMP7 (left, green) and DsRed2 (right, red) fluorescence images of hippocampal CA1 pyramidal neurons imaged 140 µm from the hippocampal surface. Arrowheads indicate two representative neurons [cells 6 and 7 in (d)] (scale bar = 50 µm). (d) Positions of 10 active neurons are indicated by red boxes in an average G-CaMP7 fluorescence image (left). Baseline-normalized G-CaMP7 fluorescence time traces for the 10 cells (right). In addition to each cellular signal, the average fluorescence signal across the whole field (Field) is shown. (e) Average G-CaMP7 fluorescence images acquired in the CA1 hippocampus at different focal depths using the ETL controlled by 0 V (left) and 0.25 V (right) voltages. The positions of representative neurons on each focal plane are indicated by red boxes (scale bar = 100 µm). (f) Baseline-normalized G-CaMP7 fluorescence time traces for the four cells shown in (e). Statistically significant fluorescence changes that are larger than five times the standard deviation of the baseline signal are indicated by asterisks. (g) Example time-lapse images of G-CaMP7 fluorescence during spontaneous activity of cell 3 are shown from top to bottom. Series of images acquired quasi-simultaneously at different depths are shown in left (0 V) and right (0.25 V) panels. Red arrows indicate cell 3 in the left panel and the corresponding position in the right panel. Their magnified views are shown in the right-hand side of each panel.

Fig. 6
Fig. 6

Fast varifocal microendoscopic imaging of spontaneous activity in amygdalar neuronal circuits in mice. (a) A coronal brain section of a Thy1-G-CaMP7-DsRed2 transgenic mouse implanted with a guide cannula for amygdalar imaging (AMY: amygdala; scale bar = 1 mm). (b) G-CaMP7 (top, green) and DsRed2 (middle, red) fluorescence images of the amygdalar surface. A merged image of the two fluorescence signals is shown at the bottom. The white dashed box delineates the area imaged in (c) (scale bar = 100 µm). (c) Average G-CaMP7 fluorescence images acquired in amygdala using the ETL controlled by 0 V (left) and 0.35 V (right) control voltages. The positions of neurons on each focal plane are indicated by red boxes (scale bar = 50 µm). (d) Baseline-normalized G-CaMP7 fluorescence time traces for the seven cells shown in (c). In addition to each cellular signal, average fluorescence signals across the whole field (Field) are shown for each plane. Statistically significant fluorescence changes that are larger than five times the standard deviation of the baseline signal are indicated by asterisks. Shaded bars represent significant field activity detected at depths of 0 V (green), 0.35 V (red), or both (gray).