Abstract

The ability to image neurons anywhere in the mammalian brain is a major goal of optical microscopy. Here we describe a minimally invasive microendoscopy system for studying the morphology and function of neurons at depth. Utilizing a guide cannula with an ultrathin wall, we demonstrated in vivo two-photon fluorescence imaging of deeply buried nuclei such as the striatum (2.5 mm depth), substantia nigra (4.4 mm depth) and lateral hypothalamus (5.0 mm depth) in mouse brain. We reported, for the first time, the observation of neuronal activity with subcellular resolution in the lateral hypothalamus and substantia nigra of head-fixed awake mice.

© 2015 Optical Society of America

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  25. W. Denk, J. H. Strickler, and W. W. Webb, “Two-photon laser scanning fluorescence microscopy,” Science 248(4951), 73–76 (1990).
    [Crossref] [PubMed]
  26. D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
    [Crossref] [PubMed]
  27. 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]

2014 (2)

J. E. Osborne and J. T. Dudman, “RIVETS: A mechanical system for in vivo and in vitro electrophysiology and imaging,” PLoS One 9(2), e89007 (2014).
[Crossref] [PubMed]

N. Ji, “The practical and fundamental limits of optical imaging in mammalian brains,” Neuron 83(6), 1242–1245 (2014).
[Crossref] [PubMed]

2013 (2)

C. Wang and 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).
[Crossref] [PubMed]

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

2012 (3)

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A. 109(1), 22–27 (2012).
[Crossref] [PubMed]

C. Wang and N. Ji, “Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture gradient refractive index lens for two-photon fluorescence endoscopy,” Opt. Lett. 37(11), 2001–2003 (2012).
[Crossref] [PubMed]

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[Crossref] [PubMed]

2011 (4)

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Y. Aponte, D. Atasoy, and S. M. Sternson, “AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training,” Nat. Neurosci. 14(3), 351–355 (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]

2010 (3)

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

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)

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

2007 (2)

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

2006 (2)

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[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]

2003 (1)

2001 (1)

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[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]

Ackerman, S. L.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Adelman, T. L.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[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.

Y. Aponte, D. Atasoy, and S. M. Sternson, “AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training,” Nat. Neurosci. 14(3), 351–355 (2011).
[Crossref] [PubMed]

Atasoy, D.

Y. Aponte, D. Atasoy, and S. M. Sternson, “AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training,” Nat. Neurosci. 14(3), 351–355 (2011).
[Crossref] [PubMed]

Attardo, A.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Baohan, A.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Barretto, R. P. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Bergner, C. G.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Betzig, E.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A. 109(1), 22–27 (2012).
[Crossref] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Bock, N. A.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Bückle, R.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

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]

Butovas, S.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Callaway, E. M.

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[Crossref] [PubMed]

Capps, G.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Cardona, A. E.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Cardona, S. M.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Chao, W.-H.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Chen, T.-W.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Chen, Y.-F.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Chen, Y.-Y.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Cho, C.-W.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[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]

Collman, F.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Cook, D. N.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[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]

Czubayko, U.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Denk, W.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[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]

Dijkstra, I. M.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[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]

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[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]

Dombrowski, S.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Dudman, J. T.

J. E. Osborne and J. T. Dudman, “RIVETS: A mechanical system for in vivo and in vitro electrophysiology and imaging,” PLoS One 9(2), e89007 (2014).
[Crossref] [PubMed]

Dutta, R.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Ehlers, A.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[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]

Gerdjikov, T. V.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[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]

Haiss, F.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[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]

Henkelman, R. M.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Hentschke, H.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Herb, J. T.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Huang, D.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Jayaraman, V.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Ji, N.

N. Ji, “The practical and fundamental limits of optical imaging in mammalian brains,” Neuron 83(6), 1242–1245 (2014).
[Crossref] [PubMed]

C. Wang and 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).
[Crossref] [PubMed]

C. Wang and N. Ji, “Pupil-segmentation-based adaptive optical correction of a high-numerical-aperture gradient refractive index lens for two-photon fluorescence endoscopy,” Opt. Lett. 37(11), 2001–2003 (2012).
[Crossref] [PubMed]

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A. 109(1), 22–27 (2012).
[Crossref] [PubMed]

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Jung, J. C.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[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. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
[Crossref] [PubMed]

Jung, S.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Kaatz, M.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[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]

Kaye, A. P.

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[Crossref] [PubMed]

Kerr, J. N.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Kerr, R. A.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Khabbaz, A. N.

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

Kidd, G.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Kim, D. S.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Kipke, D. R.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Ko, T. H.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

König, K.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

Kostenko, V.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Kovacevic, N.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Lai, H.-Y.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Lee, J.-C.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[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]

Liao, C.-H.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Lin, S.-H.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Lin, S.-Y.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Lipina, T. V.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Lira, S. A.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Littman, D. R.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Looger, L. L.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

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]

Marshel, J. H.

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[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]

Milkie, D. E.

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[Crossref] [PubMed]

Mittmann, W.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[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]

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]

Nauhaus, I.

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[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]

Orger, M. B.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Osborne, J. E.

J. E. Osborne and J. T. Dudman, “RIVETS: A mechanical system for in vivo and in vitro electrophysiology and imaging,” PLoS One 9(2), e89007 (2014).
[Crossref] [PubMed]

Pellinen, D. S.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Pioro, E. P.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Pivin, D. P.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Pulver, S. R.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Ransohoff, R. M.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Recht, L.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Renninger, S. L.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Riemann, I.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

Roder, J. C.

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

Rousche, P. J.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Sasse, M. E.

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

Sato, T. R.

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A. 109(1), 22–27 (2012).
[Crossref] [PubMed]

Schaefer, A. T.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Schenkl, S.

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

Schnitzer, M. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (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]

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. C. Jung and M. J. Schnitzer, “Multiphoton endoscopy,” Opt. Lett. 28(11), 902–904 (2003).
[Crossref] [PubMed]

Schreiter, E. R.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Schwarz, C.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[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]

Sternson, S. M.

Y. Aponte, D. Atasoy, and S. M. Sternson, “AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training,” Nat. Neurosci. 14(3), 351–355 (2011).
[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]

Stüttgen, M. C.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Sun, Y.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Svoboda, K.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[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]

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[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]

Tsang, S.

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Vetter, R. J.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Waiblinger, C.

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Wallace, D. J.

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Wang, C.

Wang, T. J.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Wardill, T. J.

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Waters, A. C.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[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]

Williams, J. C.

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

Ziv, Y.

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (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]

IEEE Trans. Biomed. Eng. (1)

P. J. Rousche, D. S. Pellinen, D. P. Pivin, J. C. Williams, R. J. Vetter, and D. R. Kipke, “Flexible polyimide-based intracortical electrode arrays with bioactive capability,” IEEE Trans. Biomed. Eng. 48(3), 361–371 (2001).
[Crossref] [PubMed]

J. Neurophysiol. (2)

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. (2)

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]

N. A. Bock, N. Kovacevic, T. V. Lipina, J. C. Roder, S. L. Ackerman, and R. M. Henkelman, “In vivo magnetic resonance imaging and semiautomated image analysis extend the brain phenotype for cdf/cdf mice,” J. Neurosci. 26(17), 4455–4459 (2006).
[Crossref] [PubMed]

J. Neurosci. Methods (1)

Y.-Y. Chen, H.-Y. Lai, S.-H. Lin, C.-W. Cho, W.-H. Chao, C.-H. Liao, S. Tsang, Y.-F. Chen, and S.-Y. Lin, “Design and fabrication of a polyimide-based microelectrode array: Application in neural recording and repeatable electrolytic lesion in rat brain,” J. Neurosci. Methods 182(1), 6–16 (2009).
[Crossref] [PubMed]

Microsc. Res. Tech. (1)

K. König, A. Ehlers, I. Riemann, S. Schenkl, R. Bückle, and M. Kaatz, “Clinical two-photon microendoscopy,” Microsc. Res. Tech. 70(5), 398–402 (2007).
[Crossref] [PubMed]

Nat. Med. (1)

R. P. J. Barretto, T. H. Ko, J. C. Jung, T. J. Wang, G. Capps, A. C. Waters, Y. Ziv, A. Attardo, L. Recht, and M. J. Schnitzer, “Time-lapse imaging of disease progression in deep brain areas using fluorescence microendoscopy,” Nat. Med. 17(2), 223–228 (2011).
[Crossref] [PubMed]

Nat. Methods (2)

N. Ji, D. E. Milkie, and E. Betzig, “Adaptive optics via pupil segmentation for high-resolution imaging in biological tissues,” Nat. Methods 7(2), 141–147 (2010).
[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. (4)

Y. Aponte, D. Atasoy, and S. M. Sternson, “AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training,” Nat. Neurosci. 14(3), 351–355 (2011).
[Crossref] [PubMed]

A. E. Cardona, E. P. Pioro, M. E. Sasse, V. Kostenko, S. M. Cardona, I. M. Dijkstra, D. Huang, G. Kidd, S. Dombrowski, R. Dutta, J.-C. Lee, D. N. Cook, S. Jung, S. A. Lira, D. R. Littman, and R. M. Ransohoff, “Control of microglial neurotoxicity by the fractalkine receptor,” Nat. Neurosci. 9(7), 917–924 (2006).
[Crossref] [PubMed]

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]

W. Mittmann, D. J. Wallace, U. Czubayko, J. T. Herb, A. T. Schaefer, L. L. Looger, W. Denk, and J. N. Kerr, “Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo,” Nat. Neurosci. 14(8), 1089–1093 (2011).
[Crossref] [PubMed]

Nature (1)

T.-W. Chen, T. J. Wardill, Y. Sun, S. R. Pulver, S. L. Renninger, A. Baohan, E. R. Schreiter, R. A. Kerr, M. B. Orger, V. Jayaraman, L. L. Looger, K. Svoboda, and D. S. Kim, “Ultrasensitive fluorescent proteins for imaging neuronal activity,” Nature 499(7458), 295–300 (2013).
[Crossref] [PubMed]

Neuron (3)

D. A. Dombeck, A. N. Khabbaz, F. Collman, T. L. Adelman, and D. W. Tank, “Imaging large-scale neural activity with cellular resolution in awake, mobile mice,” Neuron 56(1), 43–57 (2007).
[Crossref] [PubMed]

N. Ji, “The practical and fundamental limits of optical imaging in mammalian brains,” Neuron 83(6), 1242–1245 (2014).
[Crossref] [PubMed]

J. H. Marshel, A. P. Kaye, I. Nauhaus, and E. M. Callaway, “Anterior-posterior direction opponency in the superficial mouse lateral geniculate nucleus,” Neuron 76(4), 713–720 (2012).
[Crossref] [PubMed]

Opt. Express (1)

Opt. Lett. (2)

PLoS One (1)

J. E. Osborne and J. T. Dudman, “RIVETS: A mechanical system for in vivo and in vitro electrophysiology and imaging,” PLoS One 9(2), e89007 (2014).
[Crossref] [PubMed]

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

N. Ji, T. R. Sato, and E. Betzig, “Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex,” Proc. Natl. Acad. Sci. U.S.A. 109(1), 22–27 (2012).
[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]

Somatosens. Mot. Res. (1)

C. Schwarz, H. Hentschke, S. Butovas, F. Haiss, M. C. Stüttgen, T. V. Gerdjikov, C. G. Bergner, and C. Waiblinger, “The head-fixed behaving rat--procedures and pitfalls,” Somatosens. Mot. Res. 27(4), 131–148 (2010).
[Crossref] [PubMed]

Other (2)

C. Gomez-Reino, M. V. Perez, and C. Bao, Gradient-Index Optics (Berlin: Springer-Verlag 2002).

R. P. J. Barretto and M. J. Schnitzer, “In vivo optical microendoscopy for imaging cells lying deep within live tissue,” in Imaging: A Laboratory Manual, R. Yuste, ed. (Cold Spring Harbor Laboratory Press, 2011).

Supplementary Material (2)

NameDescription
» Visualization 1: AVI (3269 KB)      In vivo 3D image stack of GCaMP6+ neurons in the lateral hypothalamus of an awake mouse
» Visualization 2: AVI (20976 KB)      In vivo recording of neural activities of GCaMP6+ neurons in the mouse lateral hypothalamus under anesthetized or awake conditions

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Figures (5)

Fig. 1
Fig. 1 Schematics of the minimally invasive microendoscopy system. (a) Design of the guide cannula. Dimensions are in millimeters. (b) A mouse with guide cannula and head-bar implantation. (c) A 0.5-mm-diameter GRIN lens relays the focus of a 0.2-NA objective to a 0.5-NA focus inside a deeply buried nucleus (e.g., lateral hypothalamus). d indicates the distance between the objective focus and the top of the GRIN lens. The brain, guide cannula, and GRIN lens are drawn to scale. Scale bar: 1 mm.
Fig. 2
Fig. 2 Imaging performance of the 0.5-NA, 0.5-mm-diameter GRIN lens. (a) Focal series images (at 0.5 µm steps) of a 1-µm-diameter fluorescence bead before and after AO correction. (b) Lateral and axial signals of the focal series images in (a) measured with and without AO correction. (c) Fluorescence beads imaged over a large FOV at different focal planes by varying the image-space distance d between the air objective focus and GRIN lens. Excitation power: 15 mW. Scale bars: (a) 2 µm and (c) 20 µm.
Fig. 3
Fig. 3 Inflammatory reactions triggered by guide cannula implantation dissipate after ~4 weeks. (a) and (b) Top panels: widefield images of brain sections showing the location of an implanted guide cannula in the right hemisphere above the lateral hypothalamus. Bottom panels: confocal images of GFAP+ and IBA1+ glia (a) two and (b) four weeks after guide cannula implantation. Images from left hemisphere serve as controls of glia populations in intact brain tissue. Black scale bars: 1 mm; white scale bars: 0.1 mm.
Fig. 4
Fig. 4 Chronic in vivo images of neurons from deeply buried nuclei of head-fixed awake mice. (a) Two-photon fluorescence endomicroscopy images of neurons in lateral hypothalamus across 16 days. (b) Two-photon fluorescence endomicroscopy images of neurons in striatum across 36 days. The brain, guide cannula, and GRIN lens were drawn to scale. Black scale bar: 1 mm. White scale bar: 20 µm.
Fig. 5
Fig. 5 In vivo functional imaging of neuronal activity from deeply buried nuclei of head-fixed awake mice. (a) Left panel: two-photon fluorescence endomicroscopy images of neurons in the lateral hypothalamus; Right panel: regions of interest (ROIs) outline individual neurons. (b) Neuronal activity as measured by the calcium transient ΔF/F of neurons in (a) with the mouse first anesthetized and then awake. (c) Left panel: two-photon fluorescence endomicroscopy images of neurons in substantia nigra; Right panel: ROIs outline individual neurons. (d) Neuronal activity as measured by the calcium transient ΔF/F of neurons in (c) from an awake mouse.

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