Abstract

Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time “movies”. This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue.

© 2016 Optical Society of America

Full Article  |  PDF Article
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References

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  1. J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
    [Crossref] [PubMed]
  2. D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
    [PubMed]
  3. N. K. Logothetis and J. Pfeuffer, “On the nature of the BOLD fMRI contrast mechanism,” Magn. Reson. Imaging 22(10), 1517–1531 (2004).
    [Crossref] [PubMed]
  4. J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
    [Crossref] [PubMed]
  5. Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
    [Crossref] [PubMed]
  6. A. Grinvald and R. Hildesheim, “VSDI: a new era in functional imaging of cortical dynamics,” Nat. Rev. Neurosci. 5(11), 874–885 (2004).
    [Crossref] [PubMed]
  7. C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
    [Crossref] [PubMed]
  8. G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
    [PubMed]
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    [Crossref] [PubMed]
  10. R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  12. I. Tasaki and P. M. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992).
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    [Crossref] [PubMed]
  14. L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
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    [Crossref] [PubMed]
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    [Crossref] [PubMed]
  18. K. Furusawa, “The depolarization of crustacean nerve by stimulation or oxygen want,” J. Physiol. 67(4), 325–342 (1929).
    [Crossref] [PubMed]
  19. P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
    [Crossref] [PubMed]
  20. C. D. Derby and J. Atema, “Chemosensitivity of Walking Legs of the Lobster Homarus Americanus: Neurophysiological Response Spectrum and Thresholds,” J. Exp. Biol. 98, 303–315 (1982).
  21. J. Z. Young, “The structure of nerve fibres in cephalopods and crustacea,” Proc. R. Soc. Lond. B Biol. Sci. 121(823), 319–337 (1936).
    [Crossref]
  22. A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
    [Crossref] [PubMed]
  23. X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
    [Crossref] [PubMed]
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2015 (2)

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

A. H. Badreddine, K. J. Schoener, and I. J. Bigio, “Elucidating the temporal dynamics of optical birefringence changes in crustacean nerves,” Biomed. Opt. Express 6(10), 4165–4178 (2015).
[Crossref] [PubMed]

2014 (1)

G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
[PubMed]

2010 (1)

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

2008 (1)

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

2007 (1)

A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007).
[Crossref] [PubMed]

2005 (2)

Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
[Crossref] [PubMed]

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

2004 (3)

A. Grinvald and R. Hildesheim, “VSDI: a new era in functional imaging of cortical dynamics,” Nat. Rev. Neurosci. 5(11), 874–885 (2004).
[Crossref] [PubMed]

N. K. Logothetis and J. Pfeuffer, “On the nature of the BOLD fMRI contrast mechanism,” Magn. Reson. Imaging 22(10), 1517–1531 (2004).
[Crossref] [PubMed]

K. M. Carter, J. S. George, and D. M. Rector, “Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve,” J. Neurosci. Methods 135(1-2), 9–16 (2004).
[Crossref] [PubMed]

2003 (1)

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

2000 (1)

1997 (1)

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

1992 (1)

I. Tasaki and P. M. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992).
[Crossref] [PubMed]

1991 (1)

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

1982 (1)

C. D. Derby and J. Atema, “Chemosensitivity of Walking Legs of the Lobster Homarus Americanus: Neurophysiological Response Spectrum and Thresholds,” J. Exp. Biol. 98, 303–315 (1982).

1977 (1)

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

1976 (1)

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

1970 (1)

L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
[Crossref] [PubMed]

1969 (1)

L. B. Cohen, B. Hille, and R. D. Keynes, “Light scattering and birefringence changes during activity in the electric organ of electrophorus electricus,” J. Physiol. 203(2), 489–509 (1969).
[Crossref] [PubMed]

1968 (1)

A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
[Crossref] [PubMed]

1936 (1)

J. Z. Young, “The structure of nerve fibres in cephalopods and crustacea,” Proc. R. Soc. Lond. B Biol. Sci. 121(823), 319–337 (1936).
[Crossref]

1929 (1)

K. Furusawa, “The depolarization of crustacean nerve by stimulation or oxygen want,” J. Physiol. 67(4), 325–342 (1929).
[Crossref] [PubMed]

Atema, J.

C. D. Derby and J. Atema, “Chemosensitivity of Walking Legs of the Lobster Homarus Americanus: Neurophysiological Response Spectrum and Thresholds,” J. Exp. Biol. 98, 303–315 (1982).

Badreddine, A. H.

Barrowes, B.

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

Barthó, P.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Bigio, I. J.

Blonder, G. E.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Broussard, G. J.

G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
[PubMed]

Brzin, M.

A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
[Crossref] [PubMed]

Buzsáki, G.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Byrne, P. M. M.

I. Tasaki and P. M. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992).
[Crossref] [PubMed]

Carter, K. M.

K. M. Carter, J. S. George, and D. M. Rector, “Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve,” J. Neurosci. Methods 135(1-2), 9–16 (2004).
[Crossref] [PubMed]

Cohen, L. B.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
[Crossref] [PubMed]

L. B. Cohen, B. Hille, and R. D. Keynes, “Light scattering and birefringence changes during activity in the electric organ of electrophorus electricus,” J. Physiol. 203(2), 489–509 (1969).
[Crossref] [PubMed]

Csicsvari, J.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Darin De Lorenzo, A. J.

A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
[Crossref] [PubMed]

Davila, H. V.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Deisseroth, K.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Delehanty, J. B.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Derby, C. D.

C. D. Derby and J. Atema, “Chemosensitivity of Walking Legs of the Lobster Homarus Americanus: Neurophysiological Response Spectrum and Thresholds,” J. Exp. Biol. 98, 303–315 (1982).

Dettbarn, W. D.

A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
[Crossref] [PubMed]

Durand, R.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Efros, A. L.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Erickson, J. S.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Evans, P. D.

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

Fenno, L. E.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Foust, A.

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

Foust, A. J.

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007).
[Crossref] [PubMed]

Furusawa, K.

K. Furusawa, “The depolarization of crustacean nerve by stimulation or oxygen want,” J. Physiol. 67(4), 325–342 (1929).
[Crossref] [PubMed]

George, J. S.

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

K. M. Carter, J. S. George, and D. M. Rector, “Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve,” J. Neurosci. Methods 135(1-2), 9–16 (2004).
[Crossref] [PubMed]

Goshen, I.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Gradinaru, V.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Grinvald, A.

A. Grinvald and R. Hildesheim, “VSDI: a new era in functional imaging of cortical dynamics,” Nat. Rev. Neurosci. 5(11), 874–885 (2004).
[Crossref] [PubMed]

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Harper, R. M.

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

Harris, K. D.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Henze, D. A.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Hildesheim, R.

A. Grinvald and R. Hildesheim, “VSDI: a new era in functional imaging of cortical dynamics,” Nat. Rev. Neurosci. 5(11), 874–885 (2004).
[Crossref] [PubMed]

Hille, B.

L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
[Crossref] [PubMed]

L. B. Cohen, B. Hille, and R. D. Keynes, “Light scattering and birefringence changes during activity in the electric organ of electrophorus electricus,” J. Physiol. 203(2), 489–509 (1969).
[Crossref] [PubMed]

Huston, A. L.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Ikegaya, Y.

Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
[Crossref] [PubMed]

Jamieson, B.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Keynes, R. D.

L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
[Crossref] [PubMed]

L. B. Cohen, B. Hille, and R. D. Keynes, “Light scattering and birefringence changes during activity in the electric organ of electrophorus electricus,” J. Physiol. 203(2), 489–509 (1969).
[Crossref] [PubMed]

Kim, D.-S.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Kleinfeld, D.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Kravitz, E. A.

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

Kristensen, M. P.

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

Kushto, G.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

LaPorta, A.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Le Bon-Jego, M.

Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
[Crossref] [PubMed]

Lee, J. H.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Liang, R.

G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
[PubMed]

Logothetis, N. K.

N. K. Logothetis and J. Pfeuffer, “On the nature of the BOLD fMRI contrast mechanism,” Magn. Reson. Imaging 22(10), 1517–1531 (2004).
[Crossref] [PubMed]

Mäkinen, A. J.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

McCluskey, M. D.

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

Morgan, S.

O’Shaughnessy, T. J.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Oh, E.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Pfeuffer, J.

N. K. Logothetis and J. Pfeuffer, “On the nature of the BOLD fMRI contrast mechanism,” Magn. Reson. Imaging 22(10), 1517–1531 (2004).
[Crossref] [PubMed]

Poe, G. R.

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

Raccuia-Behling, F.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Ramakrishnan, C.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Rector, D. M.

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007).
[Crossref] [PubMed]

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

K. M. Carter, J. S. George, and D. M. Rector, “Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve,” J. Neurosci. Methods 135(1-2), 9–16 (2004).
[Crossref] [PubMed]

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

Ridgway, M.

Ross, W. N.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Rowland, C. E.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Salzberg, B. M.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Schei, J. L.

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

Schoener, K. J.

Sirota, A.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Slusher, R. E.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Stepnoski, R. A.

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Stewart, M. H.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Susumu, K.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Talamo, B. R.

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

Tasaki, I.

I. Tasaki and P. M. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992).
[Crossref] [PubMed]

Tian, L.

G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
[PubMed]

Waggoner, A. S.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Wallace, B. G.

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

Wang, C. H.

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

Wise, K. D.

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

Wolak, M. A.

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Yao, X.-C.

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

Young, J. Z.

J. Z. Young, “The structure of nerve fibres in cephalopods and crustacea,” Proc. R. Soc. Lond. B Biol. Sci. 121(823), 319–337 (1936).
[Crossref]

Yuste, R.

Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
[Crossref] [PubMed]

Zhang, F.

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Biochem. Biophys. Res. Commun. (1)

I. Tasaki and P. M. M. Byrne, “Rapid structural changes in nerve fibers evoked by electric current pulses,” Biochem. Biophys. Res. Commun. 188(2), 559–564 (1992).
[Crossref] [PubMed]

Biomed. Opt. Express (1)

Biophys. J. (1)

X.-C. Yao, A. Foust, D. M. Rector, B. Barrowes, and J. S. George, “Cross-polarized reflected light measurement of fast optical responses associated with neural activation,” Biophys. J. 88(6), 4170–4177 (2005).
[Crossref] [PubMed]

Front. Mol. Neurosci. (1)

G. J. Broussard, R. Liang, and L. Tian, “Monitoring activity in neural circuits with genetically encoded indicators,” Front. Mol. Neurosci. 7, 97 (2014).
[PubMed]

J. Exp. Biol. (1)

C. D. Derby and J. Atema, “Chemosensitivity of Walking Legs of the Lobster Homarus Americanus: Neurophysiological Response Spectrum and Thresholds,” J. Exp. Biol. 98, 303–315 (1982).

J. Membr. Biol. (1)

W. N. Ross, B. M. Salzberg, L. B. Cohen, A. Grinvald, H. V. Davila, A. S. Waggoner, and C. H. Wang, “Changes in absorption, fluorescence, dichroism, and Birefringence in stained giant axons: optical measurement of membrane potential,” J. Membr. Biol. 33(1), 141–183 (1977).
[Crossref] [PubMed]

J. Neurophysiol. (2)

J. Csicsvari, D. A. Henze, B. Jamieson, K. D. Harris, A. Sirota, P. Barthó, K. D. Wise, and G. Buzsáki, “Massively parallel recording of unit and local field potentials with silicon-based electrodes,” J. Neurophysiol. 90(2), 1314–1323 (2003).
[Crossref] [PubMed]

D. M. Rector, G. R. Poe, M. P. Kristensen, and R. M. Harper, “Light scattering changes follow evoked potentials from hippocampal Schaeffer collateral stimulation,” J. Neurophysiol. 78(3), 1707–1713 (1997).
[PubMed]

J. Neurosci. Methods (1)

K. M. Carter, J. S. George, and D. M. Rector, “Simultaneous birefringence and scattered light measurements reveal anatomical features in isolated crustacean nerve,” J. Neurosci. Methods 135(1-2), 9–16 (2004).
[Crossref] [PubMed]

J. Physiol. (4)

L. B. Cohen, B. Hille, and R. D. Keynes, “Light scattering and birefringence changes during activity in the electric organ of electrophorus electricus,” J. Physiol. 203(2), 489–509 (1969).
[Crossref] [PubMed]

L. B. Cohen, B. Hille, and R. D. Keynes, “Changes in axon birefringence during the action potential,” J. Physiol. 211(2), 495–515 (1970).
[Crossref] [PubMed]

K. Furusawa, “The depolarization of crustacean nerve by stimulation or oxygen want,” J. Physiol. 67(4), 325–342 (1929).
[Crossref] [PubMed]

P. D. Evans, E. A. Kravitz, B. R. Talamo, and B. G. Wallace, “The association of octopamine with specific neurones along lobster nerve trunks,” J. Physiol. 262(1), 51–70 (1976).
[Crossref] [PubMed]

J. Ultrastruct. Res. (1)

A. J. Darin De Lorenzo, M. Brzin, and W. D. Dettbarn, “Fine structure and organization of nerve fibers and giant axons in Homarus americanus,” J. Ultrastruct. Res. 24(5-6), 367–384 (1968).
[Crossref] [PubMed]

Magn. Reson. Imaging (1)

N. K. Logothetis and J. Pfeuffer, “On the nature of the BOLD fMRI contrast mechanism,” Magn. Reson. Imaging 22(10), 1517–1531 (2004).
[Crossref] [PubMed]

Nano Lett. (1)

C. E. Rowland, K. Susumu, M. H. Stewart, E. Oh, A. J. Mäkinen, T. J. O’Shaughnessy, G. Kushto, M. A. Wolak, J. S. Erickson, A. L. Efros, A. L. Huston, and J. B. Delehanty, “Electric Field Modulation of Semiconductor Quantum Dot Photoluminescence: Insights Into the Design of Robust Voltage-Sensitive Cellular Imaging Probes,” Nano Lett. 15(10), 6848–6854 (2015).
[Crossref] [PubMed]

Nat. Rev. Neurosci. (1)

A. Grinvald and R. Hildesheim, “VSDI: a new era in functional imaging of cortical dynamics,” Nat. Rev. Neurosci. 5(11), 874–885 (2004).
[Crossref] [PubMed]

Nature (1)

J. H. Lee, R. Durand, V. Gradinaru, F. Zhang, I. Goshen, D.-S. Kim, L. E. Fenno, C. Ramakrishnan, and K. Deisseroth, “Global and local fMRI signals driven by neurons defined optogenetically by type and wiring,” Nature 465(7299), 788–792 (2010).
[Crossref] [PubMed]

Neuroimage (1)

J. L. Schei, M. D. McCluskey, A. J. Foust, X.-C. Yao, and D. M. Rector, “Action potential propagation imaged with high temporal resolution near-infrared video microscopy and polarized light,” Neuroimage 40(3), 1034–1043 (2008).
[Crossref] [PubMed]

Neurosci. Res. (1)

Y. Ikegaya, M. Le Bon-Jego, and R. Yuste, “Large-scale imaging of cortical network activity with calcium indicators,” Neurosci. Res. 52(2), 132–138 (2005).
[Crossref] [PubMed]

Neuroscience (1)

A. J. Foust and D. M. Rector, “Optically teasing apart neural swelling and depolarization,” Neuroscience 145(3), 887–899 (2007).
[Crossref] [PubMed]

Opt. Express (1)

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

R. A. Stepnoski, A. LaPorta, F. Raccuia-Behling, G. E. Blonder, R. E. Slusher, and D. Kleinfeld, “Noninvasive detection of changes in membrane potential in cultured neurons by light scattering,” Proc. Natl. Acad. Sci. U.S.A. 88(21), 9382–9386 (1991).
[Crossref] [PubMed]

Proc. R. Soc. Lond. B Biol. Sci. (1)

J. Z. Young, “The structure of nerve fibres in cephalopods and crustacea,” Proc. R. Soc. Lond. B Biol. Sci. 121(823), 319–337 (1936).
[Crossref]

Supplementary Material (3)

NameDescription
» Visualization 1: AVI (1634 KB)      Standard Stimulus, Averaged
» Visualization 2: AVI (850 KB)      Standard Stimulus, Real-time
» Visualization 3: AVI (293 KB)      Fast Stimulus, Averaged

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Figures (6)

Fig. 1
Fig. 1 The electronic and optical setup is depicted. On the right is the optical setup used for line-illumination and imaging of nerve birefringence onto a photodiode (PD) array, and using two crossed linear polarizers (LPi and LPa). A pulse generator (PG) sends reset (RES) and clock (CLK) signals to the driver circuit to run the PD array. The driver circuit outputs the analog video (VID) signal, as well as TTL pulses for both the end-of-scan (EOS) and each pixel’s individual readout (TRIG). The first data acquisition card (National Instruments, NI DAQ 1) synchronizes the analog input for the video signal with a sample clock from TRIG, so that no pixel readout is skipped. The second data acquisition card (NI DAQ 2) relays a stimulation pulse (Stim. Trig.) to the PG, which outputs a 1-ms, 10-V pulse to the linear stimulus isolator (LSI), which sends a 1-ms, 1-mA stimulus to one end of the nerve; it also records the electrical signal from the other end of the nerve, passed through a bandpass amplifier (Amp). The electronics and data collection are controlled by LabVIEW.
Fig. 2
Fig. 2 The average of the XPS over 100 stimulus periods as a function of pixel number are shown at post-stimulus times of 10, 12 17, 32, 70 and 200 ms (A-F, respectively). The onset of the peak resulting from the compound action potential is evident (A-C) and the gradual recovery to baseline (D-F) lasts hundreds of milliseconds. The propagating peak of the XPS takes ~20 ms to travel a distance of ~2 cm. This is demonstrated in Visualization 1.
Fig. 3
Fig. 3 A random, single stimulus period is extracted from the data, and a smoothing computational filter with cutoff frequencies of 0.3 Hz and 100 Hz is applied. These data provide a demonstration of a ‘real-time’, fast tracking of the XPS signal. Timepoints of 10, 12, 17, 32, 70 and 200 ms are shown (A-D, respectively). The onset and recovery of the peak can be reliably detected without averaging. This real-time tracking is demonstrated in Visualization 2.
Fig. 4
Fig. 4 Traces of the XPS are shown for 100 stimulus-averaged periods at ~6 mm (A) and ~12 mm (B) from the stimulus. Extracted single stimulus periods (C and D) are also shown. The broadening of the peak as a function of distance and the gradual recovery to baseline are evident in both averaged and real-time signals.
Fig. 5
Fig. 5 XPS data for averaged stimulus periods at a faster stimulation rate of 14Hz are shown for post-stimulus times of 15, 20, 35 and 65 ms. The recovery of the peak occurs at a faster rate and the gradual recovery is forced to return to baseline just before the initiation of the next stimulus pulse. The temporal width of the peak is reduced. This is demonstrated in Visualization 3.
Fig. 6
Fig. 6 A) The electrical recording (black) and XPS (red) at a standard stimulation rate, 2 Hz. The nerve demonstrates an adaptive response to the faster stimulus, and no reversal of polarity, which is evident with a standard stimulation rate. B) The electrical recording (black) and XPS (red) at a faster stimulation rate, 14 Hz. The XPS peak width is reduced with a faster stimulation, which may indicate a reduction in the recruitment of axons to generate action potentials as a result of adaptation to fast stimulation. The peak of the XPS coincides with the peak of the electrical recording for both fast and standard stimulation rates.

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