Abstract

There has been recently a renewed interest in using Autofluorescence imaging (AF) of NADH and flavoproteins (Fp) to map brain activity in cortical areas. The recording of these cellular signals provides complementary information to intrinsic optical imaging based on hemodynamic changes. However, which of NADH or Fp is the best candidate for AF functional imaging is not established, and the temporal profile of AF signals is not fully understood. To bring new theoretical insights into these questions, Monte Carlo simulations of AF signals were carried out in realistic models of the rat somatosensory cortex and olfactory bulb. We show that AF signals depend on the structural and physiological features of the brain area considered and are sensitive to changes in blood flow and volume induced by sensory activation. In addition, we demonstrate the feasibility of both NADH-AF and Fp-AF in the olfactory bulb.

© 2009 Optical Society of America

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    [PubMed]
  39. F.F. Jöbsis, M. O’Connor, A. Vitale, and H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–49 (1971).
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  44. M. Jones, J. Berwick, and J. Mayhew, “Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex,” Neuroimage 15, 474–87 (2002).
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  45. Prakash, J.D. Biag, S.A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A.W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37 Suppl 1, S27–36 (2007).
    [Crossref] [PubMed]

2008 (2)

G.C. Petzold, D.F. Albeanu, T.F. Sato, and V.N. Murthy, “Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways,” Neuron 58, 897–910 (2008).
[Crossref] [PubMed]

Y. Kubota, D. Kamatani, H. Tsukano, S. Ohshima, K. Takahashi, R. Hishida, M. Kudoh, S. Takahashi, and K. Shibuki, “Transcranial photo-inactivation of neural activities in the mouse auditory cortex,” Neurosci. Res. 60, 422–30 (2008).
[Crossref] [PubMed]

2007 (7)

K.C. Reinert, W. Gao, G. Chen, and T.J. Ebner, “Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo,” J. Neurosci. Res. 85, 3221–32 (2007).
[Crossref] [PubMed]

A. Mayevsky and G.G. Rogatsky, “Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies,” Am. J. Physiol. Cell. Physiol. 292, C615–40 (2007).
[Crossref]

J.C. Nawroth, C.A. Greer, W.R. Chen, S.B. Laughlin, and G.M. Shepherd, “An energy budget for the olfactory glomerulus,” J. Neurosci. 27, 9790–800 (2007).
[Crossref] [PubMed]

E.M. Hillman, A. Devor, M.B. Bouchard, A.K. Dunn, G.W. Krauss, J. Skoch, B.J. Bacskai, A.M. Dale, and D.A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35, 89–104 (2007).
[Crossref] [PubMed]

A.M. Brennan, J.A. Connor, and C.W. Shuttleworth, “Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation,” J. Neurosci. Res. 85, 3233–43 (2007).
[Crossref] [PubMed]

T.R. Husson, A.K. Mallik, J.X. Zhang, and N.P. Issa, “Functional imaging of primary visual cortex using flavoprotein autofluorescence,” J. Neurosci. 27, 8665–75 (2007).
[Crossref] [PubMed]

Prakash, J.D. Biag, S.A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A.W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37 Suppl 1, S27–36 (2007).
[Crossref] [PubMed]

2006 (3)

A.M. Brennan, J.A. Connor, and C.W. Shuttleworth, “NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function,” J. Cereb. Blood Flow. Metab. 26, 1389–406 (2006).
[Crossref] [PubMed]

H. Gurden, N. Uchida, and Z.F. Mainen, “Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake,” Neuron 52, 335–45 (2006).
[Crossref] [PubMed]

M. Tohmi, H. Kitaura, S. Komagata, M. Kudoh, and K. Shibuki, “Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex,” J. Neurosci. 26, 11775–85 (2006).
[Crossref] [PubMed]

2004 (3)

H. Murakami, D. Kamatani, R. Hishida, T. Takao, M. Kudoh, T. Kawaguchi, R. Tanaka, and K. Shibuki, “Short-term plasticity visualized with flavoprotein autofluorescence in the somatosensory cortex of anaesthetized rats,” Eur. J. Neurosci. 19, 1352–60 (2004).
[Crossref] [PubMed]

K.C. Reinert, R.L. Dunbar, W. Gao, G. Chen, and T.J. Ebner, “Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo,” J. Neurophysiol. 92,199–211 (2004).
[Crossref] [PubMed]

B. Weber, C. Burger, M.T. Wyss, G.K. von Schulthess, F. Scheffold, and A. Buck, “Optical imaging of the spatiotemporal dynamics of cerebral blood flow and oxidative metabolism in the rat barrel cortex,” Eur. J. Neurosci. 20, 2664–70 (2004).
[Crossref] [PubMed]

2003 (5)

E. Chaigneau, M. Oheim, E. Audinat, and S. Charpak, “Two-photon imaging of capillary blood flow in olfactory bulb glomeruli,” Proc. Natl. Acad. Sci. U. S. A. 100, 13081–6 (2003).
[Crossref] [PubMed]

C.W. Shuttleworth, A.M. Brennan, and J.A. Connor, “NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices,” J Neurosci. 23, 3196–208 (2003).
[PubMed]

C.C.H. Petersen, “The barrel cortex-integrating molecular, cellular and systems physiology,” Pflugers Arch. 447, 126–34 (2003).
[Crossref] [PubMed]

K. Shibuki, R. Hishida, H. Murakami, M. Kudoh, T. Kawaguchi, M. Watanabe, S. Watanabe, T. Kouuchi, and R. Tanaka., “Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence,” J. Physiol. 549, 919–27 (2003).
[Crossref] [PubMed]

A. Devor, A. K. Dunn, M. L. Andermann, I. Ulbert, D. A. Boas, and A. M. Dale1 “Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex,” Neuron 39, 353–9 (2003).
[Crossref] [PubMed]

2002 (5)

M. Jones, J. Berwick, and J. Mayhew, “Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex,” Neuroimage 15,474–87 (2002).
[Crossref]

N. Plesnila, C. Putz, M. Rinecker, J. Wiezorrek, L. Schleinkofer, A.E. Goetz, and W.M. Kuebler, “Measurement of absolute values of hemoglobin oxygenation in the brain of small rodents by near infrared reflection spectrophotometry,” J. Neurosci. Methods 114, 107–17 (2002).
[Crossref] [PubMed]

A.N. Yaroslavsky, P.C. Schulze, I.V. Yaroslavsky, R. Schober, F. Ulrich, and H.J. Schwarzmaier, “Optical properties of selected native and coagulated human brain tissues in vitro in the visible and near infrared spectral range,” Phys. Med. Biol. 47, 2059–73 (2002).
[Crossref] [PubMed]

R.E. Anderson and F.B. Meyer, “In vivo fluorescent imaging of NADH redox state in brain,” Methods Enzymol. 352, 482–94 (2002).
[Crossref] [PubMed]

M. Jones, J. Berwick, and J. Mayhew, “Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex,” Neuroimage 15, 474–87 (2002).
[Crossref] [PubMed]

2000 (3)

M. Hashimoto, Y. Takeda, T. Sato, H. Kawahara, O. Nagano, and M. Hirakawa, “Dynamic changes of NADH fluorescence images and NADH content during spreading depression in the cerebral cortex of gerbils,” Brain. Res. 872, 294–300 (2000).
[Crossref] [PubMed]

M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl., “Physical model for the spectroscopic analysis of cortical intrinsic optical signals,” Phys. Med. Biol. 45, 3749–64 (2000).
[Crossref] [PubMed]

F. Xu, I. Kida, F. Hyder, and R.G. Shulman, “Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI,” Proc Natl Acad Sci U S A. 97, 10601–6. (2000).
[Crossref] [PubMed]

1999 (1)

J. Mayhew, Y. Zheng, Y. Hou, B. Vuksanovic, J. Berwick, S. Askew, and P. Coffey, “Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain,” Neuroimage 10, 304–26 (1999).
[Crossref] [PubMed]

1996 (1)

B.A. Johnson and M. Leon, “Spatial distribution of [14C]2-deoxyglucose uptake in the glomerular layer of the rat olfactory bulb following early odor reference learning,” J Comp Neurol. 37, 6557–66. (1996)

1995 (1)

L. Wang, S.L. Jacques, and L. Zheng, “MCML-Monte Carlo modeling of light transport in multi-layered tissues,” Comput. Methods Programs Biomed. 47, 131–46 (1995).
[Crossref] [PubMed]

1991 (1)

T.A. Woolsey, C.M. Rovainen, S.B. Cox, M.H. Henegar, G.E. Liang, D. Liu, Y.E. Moskalenko, J. Sui, and L. Wei, “Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain,” Cereb. Cortex. 6, 647–60 (1991).
[Crossref]

1989 (1)

S. A. Prahl, M. Keijzer, S. L. Jacques, and A. J. Welch, “A Monte Carlo Model of Light Propagation in Tissue,” Proc. SPIE IS 5, 102–11(1989).

1986 (1)

A. Grinvald, E. Lieke, R.D. Frostig, C.D. Gilbert, and T.N. Wiesel, “Functional architecture of cortex revealed by optical imaging of intrinsic signals,” Nature 324, 361–4 (1986).
[Crossref] [PubMed]

1979 (2)

B. Chance, B. Schoener, R. Oshino, F. Itshak, and Y. Nakase, “Oxidation-reduction ratio studies of mitochondria in freeze-trapped samples. NADH and flavoprotein fluorescence signals,” J. Biol. Chem. 254, 4764–71 (1979).
[PubMed]

R.C. Benson, R.A. Meyer, M.E. Zaruba, and G.M. McKhann, “Cellular autofluorescence-is it due to flavins?,” J. Histochem. Cytochem. 27, 44–8 (1979).
[Crossref] [PubMed]

1972 (2)

G.M. Shepherd, “Synaptic organization of the mammalian olfactory bulb,” Physiol. Rev. 52, 864–917 (1972).
[PubMed]

B. Chance, “The kinetics of flavoprotein and pyridine nucleotide oxidation in cardiac mitochondria in the presence of calcium,” FEBS Lett. 26, 315–9 (1972).
[Crossref] [PubMed]

1971 (1)

F.F. Jöbsis, M. O’Connor, A. Vitale, and H. Vreman, “Intracellular redox changes in functioning cerebral cortex. I. Metabolic effects of epileptiform activity,” J. Neurophysiol. 34, 735–49 (1971).
[PubMed]

1969 (1)

R. Scholz, R.G. Thurman, J.R. Williamson, B. Chance, and T. Bücher., “Flavin and pyridine nucleotide oxidation-reduction changes in perfused rat liver. I. Anoxia and subcellular localization of fluorescent flavoproteins,” J. Biol. Chem. 244, 2317–24 (1969).
[PubMed]

1962 (1)

B. Chance, P. Cohen, F. Jöbsis, and B. Schoener, “Intracellular oxidation-reduction states in vivo,” Science 137, 499–508 (1962).
[Crossref] [PubMed]

Agner, F.

F. Agner, “Pseudo random number generator;” http://www.agner.org/random/mother.

Albeanu, D.F.

G.C. Petzold, D.F. Albeanu, T.F. Sato, and V.N. Murthy, “Coupling of neural activity to blood flow in olfactory glomeruli is mediated by astrocytic pathways,” Neuron 58, 897–910 (2008).
[Crossref] [PubMed]

Andermann, M. L.

A. Devor, A. K. Dunn, M. L. Andermann, I. Ulbert, D. A. Boas, and A. M. Dale1 “Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex,” Neuron 39, 353–9 (2003).
[Crossref] [PubMed]

Anderson, R.E.

R.E. Anderson and F.B. Meyer, “In vivo fluorescent imaging of NADH redox state in brain,” Methods Enzymol. 352, 482–94 (2002).
[Crossref] [PubMed]

Askew, S.

J. Mayhew, Y. Zheng, Y. Hou, B. Vuksanovic, J. Berwick, S. Askew, and P. Coffey, “Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain,” Neuroimage 10, 304–26 (1999).
[Crossref] [PubMed]

Audinat, E.

E. Chaigneau, M. Oheim, E. Audinat, and S. Charpak, “Two-photon imaging of capillary blood flow in olfactory bulb glomeruli,” Proc. Natl. Acad. Sci. U. S. A. 100, 13081–6 (2003).
[Crossref] [PubMed]

Bacskai, B.J.

E.M. Hillman, A. Devor, M.B. Bouchard, A.K. Dunn, G.W. Krauss, J. Skoch, B.J. Bacskai, A.M. Dale, and D.A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35, 89–104 (2007).
[Crossref] [PubMed]

Benson, R.C.

R.C. Benson, R.A. Meyer, M.E. Zaruba, and G.M. McKhann, “Cellular autofluorescence-is it due to flavins?,” J. Histochem. Cytochem. 27, 44–8 (1979).
[Crossref] [PubMed]

Berwick, J.

M. Jones, J. Berwick, and J. Mayhew, “Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex,” Neuroimage 15, 474–87 (2002).
[Crossref] [PubMed]

M. Jones, J. Berwick, and J. Mayhew, “Changes in blood flow, oxygenation, and volume following extended stimulation of rodent barrel cortex,” Neuroimage 15,474–87 (2002).
[Crossref]

J. Mayhew, Y. Zheng, Y. Hou, B. Vuksanovic, J. Berwick, S. Askew, and P. Coffey, “Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain,” Neuroimage 10, 304–26 (1999).
[Crossref] [PubMed]

Biag, J.D.

Prakash, J.D. Biag, S.A. Sheth, S. Mitsuyama, J. Theriot, C. Ramachandra, and A.W. Toga, “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex,” Neuroimage 37 Suppl 1, S27–36 (2007).
[Crossref] [PubMed]

Boas, D. A.

A. Devor, A. K. Dunn, M. L. Andermann, I. Ulbert, D. A. Boas, and A. M. Dale1 “Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex,” Neuron 39, 353–9 (2003).
[Crossref] [PubMed]

Boas, D.A.

E.M. Hillman, A. Devor, M.B. Bouchard, A.K. Dunn, G.W. Krauss, J. Skoch, B.J. Bacskai, A.M. Dale, and D.A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35, 89–104 (2007).
[Crossref] [PubMed]

Bonhoeffer, T.

T. Bonhoeffer and A Grinvald “Optical Imaging based on intrinsic signals: the methodology” in Brain mapping; the methods”. A.W. Toga and J.C. Mazziotta, Eds. (Academic Press, Los Angeles, CA, 1996).

Bouchard, M.B.

E.M. Hillman, A. Devor, M.B. Bouchard, A.K. Dunn, G.W. Krauss, J. Skoch, B.J. Bacskai, A.M. Dale, and D.A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35, 89–104 (2007).
[Crossref] [PubMed]

Brennan, A.M.

A.M. Brennan, J.A. Connor, and C.W. Shuttleworth, “Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation,” J. Neurosci. Res. 85, 3233–43 (2007).
[Crossref] [PubMed]

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J.C. Nawroth, C.A. Greer, W.R. Chen, S.B. Laughlin, and G.M. Shepherd, “An energy budget for the olfactory glomerulus,” J. Neurosci. 27, 9790–800 (2007).
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A.M. Brennan, J.A. Connor, and C.W. Shuttleworth, “Modulation of the amplitude of NAD(P)H fluorescence transients after synaptic stimulation,” J. Neurosci. Res. 85, 3233–43 (2007).
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K.C. Reinert, W. Gao, G. Chen, and T.J. Ebner, “Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo,” J. Neurosci. Res. 85, 3221–32 (2007).
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A. Grinvald, E. Lieke, R.D. Frostig, C.D. Gilbert, and T.N. Wiesel, “Functional architecture of cortex revealed by optical imaging of intrinsic signals,” Nature 324, 361–4 (1986).
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Gao, W.

K.C. Reinert, W. Gao, G. Chen, and T.J. Ebner, “Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo,” J. Neurosci. Res. 85, 3221–32 (2007).
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A. Grinvald, E. Lieke, R.D. Frostig, C.D. Gilbert, and T.N. Wiesel, “Functional architecture of cortex revealed by optical imaging of intrinsic signals,” Nature 324, 361–4 (1986).
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N. Plesnila, C. Putz, M. Rinecker, J. Wiezorrek, L. Schleinkofer, A.E. Goetz, and W.M. Kuebler, “Measurement of absolute values of hemoglobin oxygenation in the brain of small rodents by near infrared reflection spectrophotometry,” J. Neurosci. Methods 114, 107–17 (2002).
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Greer, C.A.

J.C. Nawroth, C.A. Greer, W.R. Chen, S.B. Laughlin, and G.M. Shepherd, “An energy budget for the olfactory glomerulus,” J. Neurosci. 27, 9790–800 (2007).
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H. Murakami, D. Kamatani, R. Hishida, T. Takao, M. Kudoh, T. Kawaguchi, R. Tanaka, and K. Shibuki, “Short-term plasticity visualized with flavoprotein autofluorescence in the somatosensory cortex of anaesthetized rats,” Eur. J. Neurosci. 19, 1352–60 (2004).
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H. Murakami, D. Kamatani, R. Hishida, T. Takao, M. Kudoh, T. Kawaguchi, R. Tanaka, and K. Shibuki, “Short-term plasticity visualized with flavoprotein autofluorescence in the somatosensory cortex of anaesthetized rats,” Eur. J. Neurosci. 19, 1352–60 (2004).
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K. Shibuki, R. Hishida, H. Murakami, M. Kudoh, T. Kawaguchi, M. Watanabe, S. Watanabe, T. Kouuchi, and R. Tanaka., “Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence,” J. Physiol. 549, 919–27 (2003).
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M. Hashimoto, Y. Takeda, T. Sato, H. Kawahara, O. Nagano, and M. Hirakawa, “Dynamic changes of NADH fluorescence images and NADH content during spreading depression in the cerebral cortex of gerbils,” Brain. Res. 872, 294–300 (2000).
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S. A. Prahl, M. Keijzer, S. L. Jacques, and A. J. Welch, “A Monte Carlo Model of Light Propagation in Tissue,” Proc. SPIE IS 5, 102–11(1989).

Kida, I.

F. Xu, I. Kida, F. Hyder, and R.G. Shulman, “Assessment and discrimination of odor stimuli in rat olfactory bulb by dynamic functional MRI,” Proc Natl Acad Sci U S A. 97, 10601–6. (2000).
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E.M. Hillman, A. Devor, M.B. Bouchard, A.K. Dunn, G.W. Krauss, J. Skoch, B.J. Bacskai, A.M. Dale, and D.A. Boas, “Depth-resolved optical imaging and microscopy of vascular compartment dynamics during somatosensory stimulation,” Neuroimage 35, 89–104 (2007).
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Y. Kubota, D. Kamatani, H. Tsukano, S. Ohshima, K. Takahashi, R. Hishida, M. Kudoh, S. Takahashi, and K. Shibuki, “Transcranial photo-inactivation of neural activities in the mouse auditory cortex,” Neurosci. Res. 60, 422–30 (2008).
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Y. Kubota, D. Kamatani, H. Tsukano, S. Ohshima, K. Takahashi, R. Hishida, M. Kudoh, S. Takahashi, and K. Shibuki, “Transcranial photo-inactivation of neural activities in the mouse auditory cortex,” Neurosci. Res. 60, 422–30 (2008).
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M. Tohmi, H. Kitaura, S. Komagata, M. Kudoh, and K. Shibuki, “Enduring critical period plasticity visualized by transcranial flavoprotein imaging in mouse primary visual cortex,” J. Neurosci. 26, 11775–85 (2006).
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H. Murakami, D. Kamatani, R. Hishida, T. Takao, M. Kudoh, T. Kawaguchi, R. Tanaka, and K. Shibuki, “Short-term plasticity visualized with flavoprotein autofluorescence in the somatosensory cortex of anaesthetized rats,” Eur. J. Neurosci. 19, 1352–60 (2004).
[Crossref] [PubMed]

K. Shibuki, R. Hishida, H. Murakami, M. Kudoh, T. Kawaguchi, M. Watanabe, S. Watanabe, T. Kouuchi, and R. Tanaka., “Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence,” J. Physiol. 549, 919–27 (2003).
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M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl., “Physical model for the spectroscopic analysis of cortical intrinsic optical signals,” Phys. Med. Biol. 45, 3749–64 (2000).
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J.C. Nawroth, C.A. Greer, W.R. Chen, S.B. Laughlin, and G.M. Shepherd, “An energy budget for the olfactory glomerulus,” J. Neurosci. 27, 9790–800 (2007).
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B.A. Johnson and M. Leon, “Spatial distribution of [14C]2-deoxyglucose uptake in the glomerular layer of the rat olfactory bulb following early odor reference learning,” J Comp Neurol. 37, 6557–66. (1996)

Liang, G.E.

T.A. Woolsey, C.M. Rovainen, S.B. Cox, M.H. Henegar, G.E. Liang, D. Liu, Y.E. Moskalenko, J. Sui, and L. Wei, “Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain,” Cereb. Cortex. 6, 647–60 (1991).
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M. Kohl, U. Lindauer, G. Royl, M. Kuhl, L. Gold, A. Villringer, and U. Dirnagl., “Physical model for the spectroscopic analysis of cortical intrinsic optical signals,” Phys. Med. Biol. 45, 3749–64 (2000).
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T.A. Woolsey, C.M. Rovainen, S.B. Cox, M.H. Henegar, G.E. Liang, D. Liu, Y.E. Moskalenko, J. Sui, and L. Wei, “Neuronal units linked to microvascular modules in cerebral cortex: response elements for imaging the brain,” Cereb. Cortex. 6, 647–60 (1991).
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H. Gurden, N. Uchida, and Z.F. Mainen, “Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake,” Neuron 52, 335–45 (2006).
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T.R. Husson, A.K. Mallik, J.X. Zhang, and N.P. Issa, “Functional imaging of primary visual cortex using flavoprotein autofluorescence,” J. Neurosci. 27, 8665–75 (2007).
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J. Mayhew, Y. Zheng, Y. Hou, B. Vuksanovic, J. Berwick, S. Askew, and P. Coffey, “Spectroscopic analysis of changes in remitted illumination: the response to increased neural activity in brain,” Neuroimage 10, 304–26 (1999).
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Am. J. Physiol. Cell. Physiol. (1)

A. Mayevsky and G.G. Rogatsky, “Mitochondrial function in vivo evaluated by NADH fluorescence: from animal models to human studies,” Am. J. Physiol. Cell. Physiol. 292, C615–40 (2007).
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Cereb. Cortex. (1)

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Figures (5)

Fig.1.
Fig.1.

Multi-layer models for the SsC and OB. Left column: the SsC model is constituted of Layer I (LI) and Layer II (LII), encompassing respectively layer 1 (L1) and layer 2, 3 and 4 (L2, L3, L4). Right column: the OB model is constituted of the olfactory nerve layer (ONL), glomerular layer (GL) and underneath the glomerular layer (UGL) encompassing the external plexifom layer, mitral cell layer, internal plexiform layer and the granule cell layer. See text for further details.

Fig. 2.
Fig. 2.

Absorption of excitation light at 350 and 440 nm by SsC tissues. A- Reflected (R), transmitted (T) and absorbed (ALI and ALII correspond to absorption in LI and LII, respectively) photons expressed as a percentage of the total number of photons launched. B- Absorbed excitation photons as a function of depth in the SsC expressed as a percentage of total absorbed photons. C-Percentage of photons absorbed in L2 leading to fluorescence.

Fig. 3.
Fig. 3.

Absorption of excitation light at 350 and 440 nm by OB tissues. A- Reflected (R), transmitted (T) and absorbed (AONL, AGL and AUGL correspond to photons absorbed in ONL, GL and UGL, respectively) photons expressed as a percentage of the total number of photons launched. B- Absorbed excitation photons as a function of depth in the OB expressed as a percentage of total absorbed photons. C- Percentage of photons absorbed in GL leading to fluorescence.

Fig. 4.
Fig. 4.

Intensity of the detected AF signals emitted at 440 and 530 nm from GL and LII. A- Percentage of fluorescent photons emitted by GL and LII and detected by the optical set-up in function of its origin in depth. B- Percentage of launched fluorescent photons detected by the optical set-up at the surface of tissues. C- Simulation of images at the surface of the SsC and OB for NADH-AF and Fp-AF signals (440 and 530 nm, respectively). Intensity (I) is normalized by the maximum value of intensity at 530 nm (Imax530nm).

Fig. 5.
Fig. 5.

Influence of Δ[Hb]t on the intensity of AF signals in the SsC and OB A- Relative number of detected fluorescent photons as a function of Δ[Hb]t compared to the intensity recorded at Δ[Hb]t=0%. B- Simulation of images at the surface of the SsC for NADH and Fp-AF signals (440 nm and 530 nm, respectively) at baseline conditions with no increase in [Hb]t (Δ[Hb]t=0%, left column) compared to an activity-dependent increase in [Hb]t (maximal Δ[Hb]t=30%, right column). Intensity (I) is normalized by the maximum value of intensity at Δ[Hb]t=0% (IΔ[Hb]t=0%).

Tables (4)

Tables Icon

Table 1: Optical properties in the OB with [Hb]t values of 5.4, 7.5 and 5.4 g/l, respectively for ONL, GL,UGL

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Table 2: Optical properties in the SsC with [Hb]t values of 7.5 and 10 g/l, respectively for LI and LII

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Table 3: Hemoglobin concentration in g/l in each layer for activity-evoked Δ[Hb]t

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Table 4: Absorption coefficient in cm-1 in each layer at 440 and 520 nm for increasing Δ[Hb]t

Equations (2)

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μaHb(λ)=2 , 303×[[Hb]t×εHbR(λ)×(1S)+[Hb]t×εHbO2(λ)×S]
μa (λ)=μaHb(λ)+μacell(λ)

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