Hostname: page-component-7c8c6479df-xxrs7 Total loading time: 0 Render date: 2024-03-29T01:36:05.865Z Has data issue: false hasContentIssue false

Seeing the Brain in Action: How Multiphoton Imaging Has Advanced Our Understanding of Neuronal Function

Published online by Cambridge University Press:  06 November 2008

Grace Stutzmann*
Affiliation:
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA
Get access

Abstract

Gaining insight into how the nervous system functions is a challenge for scientists, particularly because the static morphology of the brain and the cells within tell little about how they actually work. Fixed specimens can provide critical structural information, but the jump to functional neurobiology in living cells is obviated with these preparations. In order to grasp the complexity of neuronal activity, it is necessary to observe the brain in action, from the level of subcellular signaling to the whole organism. Recent advances in nonlinear microscopy have given rise to a new era for biological research. In particular, the introduction of multiphoton excitation has drastically improved the depth and speed to which we can probe brain function. In order to better appreciate recent contributions of multiphoton microscopy to our current and future understanding of biological systems, an historical awareness of past microscopy applications is useful.

Type
Multiphoton Microscopy–Special Section
Copyright
Copyright © Microscopy Society of America 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Banghart, M., Borges, K., Isacoff, E., Trauner, D. & Kramer, R. (2004). Light-activated ion channels for remote control of neuronal firing. Nat Neurosci 7(12), 13811386.CrossRefGoogle ScholarPubMed
Blair, H., Schafe, G., Bauer, E., Rodrigues, S. & LeDoux, J. (2001). Synaptic plasticity in the lateral amygdala: A cellular hypothesis of fear conditioning. Learn Mem 8(5), 229242.CrossRefGoogle ScholarPubMed
Blitzer, R., Iyengar, R. & Landau, E. (2005). Postsynaptic signaling networks: Cellular cogwheels underlying long-term plasticity. Biol Psychiatry 57(2), 113119.CrossRefGoogle ScholarPubMed
Boyden, E.S., Zhang, F., Bamberg, E., Nagel, G. & Deisseroth, K. (2005). Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8(9), 12631268.CrossRefGoogle ScholarPubMed
Bozza, T., McGann, J., Mombaerts, P. & Wachowiak, M. (2004). In vivo imaging of neuronal activity by targeted expression of a genetically encoded probe in the mouse. Neuron 42(1), 921.CrossRefGoogle ScholarPubMed
Cajal, S.R. (1888). Estructura de los centros nerviosos de las aves. Rev Trim Histol Norm Patol 1, 110.Google Scholar
Cajal, S.R. (1911). Histologie du systeme nerveux de l'homme et des vertébrés, vol. 2, pp. 519598. Paris: Maloine.Google Scholar
Callamaras, N. & Parker, I. (1999). Construction of a confocal microscope for real-time x-y and x-z imaging. Cell Calcium 26(6), 271279.CrossRefGoogle ScholarPubMed
Chu, S., Tai, S., Ho, C., Lin, C. & Sun, C. (2005). High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy. Microsc Res Tech 66(4), 193197.CrossRefGoogle ScholarPubMed
Denk, W., Delaney, K., Gelperin, A., Kleinfeld, D., Strowbridge, B., Tank, D. & Yuste, R. (1994). Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy. J Neurosci Methods 54(2), 151162.CrossRefGoogle ScholarPubMed
Denk, W., Strickler, J. & Webb, W. (1990). Two-photon laser scanning fluorescence microscopy. Science 248(4951), 7376.CrossRefGoogle ScholarPubMed
Dombeck, D., Sacconi, L., Blanchard-Desce, M. & Webb, W. (2005). Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy. J Neurophysiol 94(5), 36283636.CrossRefGoogle ScholarPubMed
Dumitriu, D., Cossart, R., Huang, J. & Yuste, R. (2006). Correlation between axonal morphologies and synaptic input kinetics of interneurons from mouse visual cortex. Cereb Cortex 17(1), 8191.CrossRefGoogle ScholarPubMed
Fujita, K., Nakamura, O., Kaneko, T., Kawata, S., Oyamada, M. & Takamatsu, T. (1999). Real-time imaging of two-photon-induced fluorescence with a microlens-array scanner and a regenerative amplifier. J Microsc 194(Pts 2–3), 528531.CrossRefGoogle Scholar
Garcia-Alloza, M. & Bacskai, B.J. (2004). Techniques for brain imaging in vivo. Neuromol Med 6(1), 6578.CrossRefGoogle ScholarPubMed
Gobel, W., Kerr, J., Nimmerjahn, A. & Helmchen, F. (2004). Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective. Opt Lett 29(21), 25212523.CrossRefGoogle Scholar
Göppert-Mayer, M. (1931). Über Elementarakte mit zwei Quantensprüngen. Ann Phys (Leipzig) 9, 273294.CrossRefGoogle Scholar
Gray, E.G. (1959). Electron microscopy of synaptic contacts on dendrite spines of the cerebral cortex. Nature 183, 15921593.CrossRefGoogle ScholarPubMed
Guillery, R. (2000). Early electron microscopic observations of synaptic structures in the cerebral cortex: A view of the contributions made by George Gray (1924–1999). Trends Neurosci 23(12), 594598.CrossRefGoogle Scholar
Halbhuber, K.J. & Konig, K. (2003). Modern laser scanning microscopy in biology, biotechnology and medicine. Ann Anat 185(1), 120.CrossRefGoogle ScholarPubMed
Heim, N. & Griesbeck, O. (2004). Genetically encoded indicators of cellular calcium dynamics based on troponin C and green fluorescent protein. J Biol Chem 279(14), 1428014286.CrossRefGoogle ScholarPubMed
Hell, S. & Andresen, V. (2001). Space-multiplexed multifocal nonlinear microscopy. J Microsc 202(Pt 3), 457463.CrossRefGoogle ScholarPubMed
Helmchen, F. & Denk, W. (2005). Deep tissue two-photon microscopy. Nat Methods 12, 932940.CrossRefGoogle Scholar
Helmchen, F., Fee, M., Tank, D. & Denk, W. (2001). A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals. Neuron 31(6), 903912.CrossRefGoogle ScholarPubMed
Hensch, T. (2005). Critical period mechanisms in developing visual cortex. Curr Top Dev Biol 69, 215237.CrossRefGoogle ScholarPubMed
Hirase, H., Nikolenko, V., Goldberg, J.H. & Yuste, R. (2002). Multiphoton stimulation of neurons. J Neurobiol 51, 237247.CrossRefGoogle ScholarPubMed
Holscher, C., Schnee, A., Dahmen, H., Setia, L. & Mallot, H. (2005). Rats are able to navigate in virtual environments. J Exp Biol 208(Pt 3), 561569.CrossRefGoogle ScholarPubMed
Holtmaat, A., Trachtenberg, J., Wilbrecht, L., Shepherd, G., Zhang, X., Knott, G. & Svoboda, K. (2005). Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45(2), 279291.CrossRefGoogle ScholarPubMed
Huang, S., Heikal, A. & Webb, W. (2002). Two-photon fluorescence spectroscopy and microscopy of NAD(P)H and flavoprotein. Biophys J 82(5), 28112825.CrossRefGoogle ScholarPubMed
Iyer, V., Hoogland, T. & Saggau, P. (2006). Fast functional imaging of single neurons using random-access multiphoton (RAMP) microscopy. J Neurophysiol 95(1), 535545.CrossRefGoogle ScholarPubMed
Jung, J., Mehta, A., Aksay, E., Stepnoski, R. & Schnitzer, M. (2004). In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. J Neurophysiol 92(5), 31213133.CrossRefGoogle ScholarPubMed
Kalb, J., Nielsen, T., Fricke, M., Egelhaaf, M. & Kurtz, R. (2004). In vivo two-photon laser-scanning microscopy of Ca2+ dynamics in visual motion-sensitive neurons. Biochem Biophys Res Commun 316(2), 341347.CrossRefGoogle ScholarPubMed
Kao, J. & Freilich, D. (2004). Reagents and method for spatio-temporal control of gene expression by illumination. U.S. Patent 6803479.Google Scholar
Kasischke, K., Vishwasrao, H., Fisher, P., Zipfel, W. & Webb, W. (2004). Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305(5680), 99103.CrossRefGoogle ScholarPubMed
Kleinfeld, D. & Griesbeck, O. (2005). From art to engineering? The rise of in vivo mammalian electrophysiology via genetically targeted labeling and nonlinear imaging. PLoS Biol 3(10), e355.CrossRefGoogle ScholarPubMed
Kurtz, R., Fricke, M., Kalb, J., Tinnefeld, P. & Sauer, M. (2006). Application of multiline two-photon microscopy to functional in vivo imaging. J Neurosci Meth 151(2), 276286.CrossRefGoogle ScholarPubMed
Lechleiter, J., Lin, D. & Sieneart, I. (2002). Multi-photon laser scanning microscopy using an acoustic optical deflector. Biophys J 83(4), 22922299.CrossRefGoogle ScholarPubMed
Levene, M., Dombeck, D., Kasischke, K., Molloy, R. & Webb, W. (2004). In vivo multiphoton microscopy of deep brain tissue. J Neurophysiol 91(4), 19081912.CrossRefGoogle ScholarPubMed
Li, Z., Burrone, J., Tyler, W.J., Hartman, K.N., Albeanu, D.F. & Murthy, V.N. (2005). Synaptic vesicle recycling studied in transgenic mice expressing synaptopHluorin. PNAS 102, 61316136.CrossRefGoogle ScholarPubMed
Mainen, Z., Malinow, R. & Svoboda, K. (1999). Synaptic calcium transients in single spines indicate that NMDA receptors are not saturated. Nature 399(6732), 151155.CrossRefGoogle Scholar
Majewska, A., Newton, J. & Sur, M. (2006). Remodeling of synaptic structure in sensory cortical areas in vivo. J Neurosci 26(11), 30213029.CrossRefGoogle ScholarPubMed
Majewska, A. & Sur, M. (2003). Motility of dendritic spines in visual cortex in vivo: Changes during the critical period and effects of visual deprivation. Proc Natl Acad Sci 100(26), 1602416029.CrossRefGoogle ScholarPubMed
Maren, S. (1999). Long-term potentiation in the amygdala: A mechanism for emotional learning and memory. Trends Neurosci 12, 561567.CrossRefGoogle Scholar
Margrie, T., Meyer, A., Caputi, A., Monyer, H., Hasan, M., Schaefer, A., Denk, W. & Brecht, M. (2003). Targeted whole-cell recordings in the mammalian brain in vivo. Neuron 39, 911918.CrossRefGoogle ScholarPubMed
Miyawaki, A., Griesbeck, O., Heim, R. & Tsien, R. (1999). Dynamic and quantitative Ca2+ measurements using improved cameleons. Proc Natl Acad Sci 96(5), 21352140.CrossRefGoogle ScholarPubMed
Nagerl, U., Eberhorn, N., Cambridge, S. & Bonhoeffer, T. (2004). Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 44, 759767.CrossRefGoogle ScholarPubMed
Nguyen, Q., Callamaras, N. & Parker, I. (2001). Construction of a two-photon microscope for video-rate Ca2+ imaging. Cell Calcium 30(6), 383393.CrossRefGoogle Scholar
Nuriya, M., Jiang, J., Nemet, B., Eisenthal, K.B. & Yuste, R. (2006). Imaging membrane potential in dendritic spines. Proc Natl Acad Sci 103(3), 786790.CrossRefGoogle ScholarPubMed
Oertner, T. (2002). Functional imaging of single synapses in brain slices. Exp Physiol 87(6), 733736.CrossRefGoogle ScholarPubMed
Oertner, T., Sabatini, B., Nimchinsky, E. & Svoboda, K. (2002). Facilitation at single synapses probed with optical quantal analysis. Nat Neurosci 7, 657664.CrossRefGoogle Scholar
Oheim, M., Beaurepaire, E., Chaigneau, E., Mertz, J. & Charpak, S. (2001). Two-photon microscopy in brain tissue: Parameters influencing the imaging depth. J Neurosci Methods 111, 2937.CrossRefGoogle ScholarPubMed
Portera-Cailliau, C., Weimer, R., De Paola, V., Caroni, P. & Svoboda, K. (2005). Diverse modes of axon elaboration in the developing neocortex. PLoS Biol 8, 272.CrossRefGoogle Scholar
Reddy, G. & Saggau, P. (2005). Fast three-dimensional laser scanning scheme using acousto-optic deflectors. J Biomed Opt 10(6), 064038.CrossRefGoogle ScholarPubMed
Roorda, R., Hohl, T., Toledo-Crow, R. & Miesenbock, G. (2004). Video-rate nonlinear microscopy of neuronal membrane dynamics with genetically encoded probes. J Neurophysiol 92(1), 609621.CrossRefGoogle ScholarPubMed
Sacconi, L., Froner, E., Antolini, R., Taghizadeh, M., Choudhury, A. & Pavone, F. (2003). Multiphoton multifocal microscopy exploiting a diffractive optical element. Opt Lett 28(20), 19181920.CrossRefGoogle ScholarPubMed
Salomé, R., Kremer, Y., Dieudonné, S., Léger, J-F., Krichevsky, O., Wyart, C., Chatenay, D. & Bourdieu, L. (2006). Ultrafast random-access scanning in two-photon microscopy using acousto-optic deflectors. J Neurosci Methods 154(1–2), 161174.CrossRefGoogle ScholarPubMed
Sanderson, M. (2004). Acquisition of multiple real-time images for laser scanning microscopy. Microsc Anal 18(4), 14.Google Scholar
Segal, M. (2002). Changing views of Cajal's neuron: The case of the dendritic spine. Prog Brain Res 136, 101107.CrossRefGoogle ScholarPubMed
Skala, M.C., Squirrell, J.M., Vrotsos, K.M., Eickhoff, J.C., Gendron-Fitzpatrick, A., Eliceiri, K.W. & Ramanujam, N. (2005). Multiphoton microscopy of endogenous fluorescence differentiates normal, precancerous, and cancerous squamous epithelial tissues. Cancer Res 65(4), 11801186.CrossRefGoogle ScholarPubMed
Skoch, J., Hickey, G., Kajdasz, S., Hyman, B. & Bacskai, B. (2005). In vivo imaging of amyloid-beta deposits in mouse brain with multiphoton microscopy. Methods Mol Biol 299, 349363.Google ScholarPubMed
Spires, T., Meyer-Luehmann, M., Stern, E., McLean, P., Skoch, J., Nguyen, P., Bacskai, B. & Hyman, B. (2005). Dendritic spine abnormalities in amyloid precursor protein transgenic mice demonstrated by gene transfer and intravital multiphoton microscopy. J Neurosci 25(31), 72787287.CrossRefGoogle ScholarPubMed
Stettler, D., Yamahachi, H., Li, W., Denk, W. & Gilbert, C. (2006). Axons and synaptic boutons are highly dynamic in adult visual cortex. Neuron 49(6), 877887.CrossRefGoogle ScholarPubMed
Straub, M., Lodemann, P., Holroyd, P., Jahn, R. & Hell, S. (2000). Live cell imaging by multifocal multiphoton microscopy. Eur J Cell Biol 79(10), 726734.CrossRefGoogle ScholarPubMed
Stutzmann, G.E., LaFerla, F. & Parker, I. (2003). Ca2+ signaling in mouse cortical neurons studied by two-photon imaging and photoreleased inositol triphosphate. J Neurosci 23(3), 758765.CrossRefGoogle ScholarPubMed
Stutzmann, G.E. & Parker, I. (2005). Dynamic multiphoton imaging: A live view from cells to systems. Physiol 20, 1521.CrossRefGoogle ScholarPubMed
Tal, E., Oron, D. & Silberberg, Y. (2005). Improved depth resolution in video-rate line-scanning multiphoton microscopy using temporal focusing. Opt Lett 30(13), 16861688.CrossRefGoogle ScholarPubMed
Theer, P., Hasan, M.T. & Denk, W. (2003). Two-photon imaging to a depth of 1000 μm in living brains by use of a Ti: Al2O3 regenerative amplifier. Opt Lett 28, 10221024.CrossRefGoogle Scholar
Thompson, S., Kao, J., Kramer, R., Poskanzer, K., Silver, R., Digregorio, D. & Wang, S. (2005). Flashy science: Controlling neural function with light. J Neurosci 25(45), 1035810365.CrossRefGoogle ScholarPubMed
Trachtenberg, J., Chen, B., Knott, G., Feng, G., Sanes, J., Welker, E. & Svoboda, K. (2002). Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420(6917), 788794.CrossRefGoogle ScholarPubMed
Waters, J. & Helmchen, F. (2004). Boosting of action potential backpropagation by neocortical network activity I. J Neurosci 24(49), 1112711136.CrossRefGoogle Scholar
Yasuda, R., Harvey, C., Zhong, H., Sobczyk, A., van Aelst, L. & Svoboda, K. (2006). Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging. Nat Neurosci 9(2), 283291.CrossRefGoogle ScholarPubMed
Zipfel, W., Williams, R., Christie, R., Nikitin, A., Hyman, B. & Webb, W. (2003). Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc Natl Acad Sci 100(12), 70757080.CrossRefGoogle ScholarPubMed
Zuo, Y., Lin, A., Chang, P. & Gan, W. (2005). Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46(2), 181189.CrossRefGoogle ScholarPubMed