Imaging in vivo: Watching the brain in action

Nature Reviews Neuroscience

Volumn 9, Issue 3, 2008, Pages 195-205

  Kerr, Jason N D ^a,b   Denk, Winfried ^b  

^a MAX PLANCK INSTITUTE FOR BIOLOGICAL CYBERNETICS   (Germany)

^b MAX PLANCK INSTITUTE FOR MEDICAL RESEARCH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CONTRAST MEDIUM;

BRAIN FUNCTION; COGNITION; CONSCIOUSNESS; FLUORESCENCE; HUMAN; IN VIVO STUDY; MULTIPHOTON MICROSCOPY; NERVE CELL NETWORK; NEUROIMAGING; PERCEPTION; PRIORITY JOURNAL; REVIEW;

ANIMALS; BRAIN; BRAIN MAPPING; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MAGNETIC RESONANCE IMAGING; MODELS, NEUROLOGICAL; NEURONS;

EID: 39549113171     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn2338     Document Type: Review

References (162)

1. Dobell, C. Antony van Leeuwenhoek and his "Little Animals" (John Bale, Sons and Danielsson, London, 1932).
2. Brown, R. A brief account of microscopical observations made in the months of June, July and August, 1827, on the particles contained in the pollen of plants; and on the general existence of active molecules in organic and inorganic bodies. Phil. Mag. 4, 161-173 (1828).
3. Callaghan, P. T. Principles of Nuclear Magnetic Resonance Microscopy (Clarendon, 1991).
4. Schmidt, K. C. & Smith, C. B. Resolution, sensitivity and precision with autoradiography and small animal positron emission tomography: implications for functional brain imaging in animal research. Nucl. Med. Biol. 32, 719-725 (2005).
5. Romans, L. E. Introduction to Computed Tomography (Lippincott, Williams & Wilkins, London, 1995).
6. Fujimoto, J. G. Optical coherence tomography for ultrahigh resolution in vivo imaging. Nature Biotechnol. 21, 1361-1367 (2003).
7. Denk, W., Strickler, J. H. & Webb, W. W. Two-photon laser scanning fluorescence microscopy. Science 248, 73-76 (1990). This study provided the first demonstration that two-photon excitation can be used to image fluorescently stained living cells and cellular substructures.
8. Denk, W. et al. Anatomical and functional imaging of neurons using 2-photon laser scanning microscopy. J. Neurosci. Methods 54, 151-162 (1994).
9. Denk, W. Two-photon excitation in functional biological imaging. J. Biomed. Opt. 1, 296-304 (1996).
10. Denk, W. & Svoboda, K. Photon upmanship: why multiphoton imaging is more than a gimmick. Neuron 18, 351-357 (1997).
11. Helmchen, F. & Denk, W. Deep tissue two-photon microscopy. Nature Methods 2, 932-940 (2005). This reference and reference 10 are important technically orientated reviews of the application of two-photon excitation to neurobiology, and provide a good introduction to the technique for a general readership.
12. Williams, R. M., Piston, D. W. & Webb, W. W. 2-photon molecular-excitation provides intrinsic 3-dimensional resolution for laser-based microscopy and microphotochemistry. FASEB J. 8, 804-813 (1994).
13. Denk, W., Piston, D. W. & Webb, W. W. in The Handbook of Confocal Microscopy (ed. Pawley, J.) 445-458 (Plenum, New York, 1995).
14. Zipfel, W. R., Williams, R. M. & Webb, W. W. Nonlinear magic: multiphoton microscopy in the biosciences. Nature Biotechnol. 21, 1368-1376 (2003).
15. Diaspro, A., Chirico, G. & Collini, M. Two-photon fluorescence excitation and related techniques in biological microscopy. Q. Rev. Biophys. 38, 97-166 (2005).
16. Oheim, M., Michael, D. J., Geisbauer, M., Madsen, D. & Chow, R. H. Principles of two-photon excitation fluorescence microscopy and other nonlinear imaging approaches. Adv. Drug Deliv. Rev. 58, 788-808 (2006).
17. Svoboda, K. & Yasuda, R. Principles of two-photon excitation microscopy and its applications to neuroscience. Neuron 50, 823-839 (2006).
18. Helmchen, F., Svoboda, K., Denk, W. & Tank, D. W. In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nature Neurosci. 2, 989-996 (1999).
19. Svoboda, K., Helmchen, F., Denk, W. & Tank, D. W. Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo. Nature Neurosci. 2, 65-73 (1999).
20. Svoboda, K., Denk, W., Kleinfeld, D. & Tank, D. W. In vivo dendritic calcium dynamics in neocortical pyramidal neurons. Nature 385, 161-165 (1997).
21. Grutzendler, J., Kasthuri, N. & Gan, W. B. Long-term dendritic spine stability in the adult cortex. Nature 420, 812-816 (2002).
22. Trachtenberg, J. T. et al. Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex. Nature 420, 788-794 (2002). This reference and reference 21 used MPM in combination with genetically labelled neurons to follow changes in dendritic spine morphology over many months. This enabled the quantification of spine turnover rates (see also references 23-26 and 135).
23. Xu, H. T., Pan, F., Yang, G. & Gan, W. B. Choice of cranial window type for in vivo imaging affects dendritic spine turnover in the cortex. Nature Neurosci. 10, 549-551 (2007).
24. Knott, G. W., Holtmaat, A., Wilbrecht, L., Welker, E. & Svoboda, K. Spine growth precedes synapse formation in the adult neocortex in vivo. Nature Neurosci. 9, 1117-1124 (2006).
25. Grutzendler, J. & Gan, W. B. Two-photon imaging of synaptic plasticity and pathology in the living mouse brain. NeuroRx 3, 489-496 (2006).
26. Zuo, Y., Yang, G., Kwon, E. & Gan, W. B. Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex. Nature 436, 261-265 (2005).
27. Portera-Cailliau, C., Weimer, R. M., De Paola, V., Caroni, P. & Svoboda, K. Diverse modes of axon elaboration in the developing neocortex. PloS Biol. 3, 1473-1487 (2005).
28. Holtmaat, A. J. et al. Transient and persistent dendritic spines in the neocortex in vivo. Neuron 45, 279-291 (2005).
29. Stettler, D. D., Yamahachi, H., Li, W., Denk, W. & Gilbert, C. D. Axons and synaptic boutons are highly dynamic in adult visual cortex. Neuron 49, 877-887 (2006).
30. 2+-indicator dyes were tried.
31. 2+ transients measured in populations of bulk-loaded neurons (see also references 35, 103 and 155).
32. 2+ imaging, this study showed that neurons in the cat visual cortex are precisely arranged according to their preferred orientation and direction, but that neurons in the rat visual cortex are not (see also reference 33).
33. Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925-928 (2006).
34. Mrsic-Flogel, T. D. et al. Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity. Neuron 54, 961-972 (2007).
35. Kerr, J. N. et al. Spatial organization of neuronal population responses in layer 2/3 of rat barrel cortex. J. Neurosci. 27, 13316-13328 (2007).
36. Gabriel, M. A system for multiple unit recording during avoidance behavior of the rabbit. Physiol. Behav. 12, 145-148 (1974).
37. Kruger, J. & Bach, M. Simultaneous recording with 30 microelectrodes in monkey visual cortex. Exp. Brain Res. 41, 191-194 (1981).
38. Shoham, S., O'Connor D, H. & Segev, R. How silent is the brain: is there a "dark matter" problem in neuroscience? J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 192, 777-784 (2006).
39. Hell, S. W. Far-field optical nanoscopy. Science 316, 1153-1158 (2007).
40. Frostig, R. D., Lieke, E. E., Ts'o, D. Y. & Grinvald, A. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals. Proc. Natl Acad. Sci. USA 87, 6082-6086 (1990).
41. Grinvald, A., Frostig, R. D., Siegel, R. M. & Bartfeld, E. High-resolution optical imaging of functional brain architecture in the awake monkey. Proc. Natl Acad. Sci. USA 88, 11559-11563 (1991).
42. Grinvald, A., Lieke, E., Frostig, R. D., Gilbert, C. D. & Wiesel, T. N. Functional architecture of cortex revealed by optical imaging of intrinsic signals. Nature 324, 361-364 (1986).
43. Huang, D. et al. Optical coherence tomography. Science 254, 1178-1181 (1991).
44. Mertz, J. Nonlinear microscopy: new techniques and applications. Curr. Opin. Neurobiol. 14, 610-616 (2004).
45. Franken, P. A. & Ward, J. F. Optical harmonics and nonlinear phenomena. Rev. Mod. Phys. 35, 23-39 (1963).
46. Minsky, M. Microscopy apparatus. US patent 3013467 (1961).
47. Centonze, V. E. & White, J. G. Multiphoton excitation provides optical sections from deeper within scattering specimens than confocal imaging. Biophys. J. 75, 2015-2024 (1998).
48. Squirrell, J. M., Wokosin, D. L., White, J. G. & Bavister, B. D. Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability. Nature Biotechnol. 17, 763-767 (1999).
49. Voie, A. H., Burns, D. H. & Spelman, F. A. Orthogonalplane fluorescence optical sectioning - 3-dimensional imaging of macroscopic biological specimens. J. Microsc. 170, 229-236 (1993).
50. Voie, A. H. Imaging the intact guinea pig tympanic bulla by orthogonal-plane fluorescence optical sectioning microscopy. Hear. Res. 171, 119-128 (2002).
51. Huisken, J., Swoger, J., Del Bene, F., Wittbrodt, J. & Stelzer, E. H. K. Optical sectioning deep inside live embryos by selective plane illumination microscopy. Science 305, 1007-1009 (2004).
52. Creutzfeldt, O. D., Watanabe, S. & Lux, H. D. Relations between EEG phenomena and potentials of single cortical cells. I. Evoked responses after thalamic and erpicortical stimulation. Electroencephalogr. Clin. Neurophysiol. 20, 1-18 (1966).
53. Watanabe, S., Konishi, M. & Creutzfeldt, O. D. Postsynaptic potentials in the cat's visual cortex following electrical stimulation of afferent pathways. Exp. Brain Res. 1, 272-283 (1966).
54. Eccles, J. C., Llinas, R. & Sasaki, K. The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum. J. Physiol. 182, 268-296 (1966).
55. Jagadeesh, B., Gray, C. M. & Ferster, D. Visually evoked oscillations of membrane potential in cells of cat visual cortex. Science 257, 552-554 (1992).
56. Brecht, M. & Sakmann, B. Whisker maps of neuronal subclasses of the rat ventral posterior medial thalamus, identified by whole-cell voltage recording and morphological reconstruction. J. Physiol. 538, 495-515 (2002).
57. Margrie, T. W., Brecht, M. & Sakmann, B. In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch. 444, 491-498 (2002).
58. Fee, M. S. Active stabilization of electrodes for intracellular recording in awake behaving animals. Neuron 27, 461-468 (2000).
59. Crochet, S. & Petersen, C. C. Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nature Neurosci. 9, 608-610 (2006).
60. Lee, A. K., Manns, I. D., Sakmann, B. & Brecht, M. Whole-cell recordings in freely moving rats. Neuron 51, 399-407 (2006).
61. Wilson, C. J. & Groves, P. M. Spontaneous firing patterns of identified spiny neurons in the rat neostriatum. Brain Res. 220, 67-80 (1981).
62. Wilson, C. J. & Kawaguchi, Y. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. J. Neurosci. 16, 2397-2410 (1996).
63. Markram, H., Lubke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. 500, 409-440 (1997).
64. Magee, J. C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209-213 (1997).
65. Larkum, M. E., Zhu, J. J. & Sakmann, B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature 398, 338-341 (1999).
66. Cossart, R., Lkegaya, Y. & Yuste, R. Calcium imaging of cortical networks dynamics. Cell Calcium 37, 451-457 (2005).
67. Grinvald, A., Anglister, L., Freeman, J. A., Hildesheim, R. & Manker, A. Real-time optical imaging of naturally evoked electrical activity in intact frog brain. Nature 308, 848-850 (1984).
68. Shoham, D. et al. Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes. Neuron 24, 791-802 (1999). This paper, together with reference 67, described the use of voltage-sensitive dyes for imaging activity from large areas of the cortex in both awake and anaesthetized animals. The approach was then complemented with simultaneous electrical recordings (see reference 69).
69. Arieli, A., Sterkin, A., Grinvald, A. & Aertsen, A. Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses. Science 273, 1868-1871 (1996).
70. Kenet, T., Bibitchkov, D., Tsodyks, M., Grinvald, A. & Arieli, A. Spontaneously emerging cortical representations of visual attributes. Nature 425, 954-956 (2003).
71. Xu, W., Huang, X., Takagaki, K. & Wu, J. Y. Compression and reflection of visually evoked cortical waves. Neuron 55, 119-129 (2007).
72. Petersen, C. C., Grinvald, A. & Sakmann, B. Spatiotemporal dynamics of sensory responses in layer 2/3 of rat barrel cortex measured in vivo by voltage-sensitive dye imaging combined with wholecell voltage recordings and neuron reconstructions. J. Neurosci. 23, 1298-1309 (2003).
73. Grinvald, A. & Hildesheim, R. VSDI: a new era in functional imaging of cortical dynamics. Nature Rev. Neurosci. 5, 874-885 (2004).
74. Arieli, A. & Grinvald, A. Optical imaging combined with targeted electrical recordings, microstimulation, or tracer injections. J. Neurosci. Methods 116, 15-28 (2002).
75. Civillico, E. F. & Contreras, D. Comparison of responses to electrical stimulation and whisker deflection using two different voltage-sensitive dyes in mouse barrel cortex in vivo. J. Membr. Biol. 208, 171-182 (2005).
76. Ogawa, S. et al. intrinsic signal changes accompanying sensory stimulation - functional brain mapping with magnetic-resonance-imaging. Proc. Natl Acad. Sci. USA 89, 5951-5955 (1992).
77. Hubener, G., Lambacher, A. & Fromherz, P. Anellated hemicyanine dyes with large symmetrical solvatochromism of absorption and fluorescence. J. Phys. Chem. B 107, 7896-7902 (2003).
78. Kuhn, B., Fromherz, P. & Denk, W. High sensitivity of Stark-shift voltage-sensing dyes by one- or two-photon excitation near the red spectral edge. Biophys. J. 87, 631-639 (2004).
79. Waters, J. & Helmchen, F. Boosting of action potential backpropagation by neocortical network activity in vivo. J. Neurosci. 24, 11127-11136 (2004).
80. 2+ influx into dendritic tufts of layer 2/3 neocortical pyramidal neurons in vitro and in vivo. J. Neurosci. 23, 8558-8567 (2003).
81. Charpak, S., Mertz, J., Beaurepaire, E., Moreaux, L. & Delaney, K. Odor-evoked calcium signals in dendrites of rat mitral cells. Proc. Natl Acad. Sci. USA 98, 1230-1234 (2001).
82. Stuart, G., Spruston, N., Sakmann, B. & Hausser, M. Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci. 20, 125-131 (1997).
83. Hausselt, S. E., Euler, T., Detwiler, P. B. & Denk, W. A dendrite-autonomous mechanism for direction selectivity in retinal starburst amacrine cells. PLoS Biol. 5, e185 (2007).
84. 2+- sensitive dye in the awake, head-fixed mouse. The mice were trained to walk on a rotating sphere while neuronal populations were simultaneously imaged.
85. Helmchen, F., Fee, M. S., Tank, D. W. & Denk, W. A miniature head-mounted two-photon microscope. High-resolution brain imaging in freely moving animals. Neuron 31, 903-912 (2001). This paper introduced a new method for imaging that provided cellular resolution in the awake, behaving rodent.
86. Flusberg, B. A., Jung, J. C., Cocker, E. D., Anderson, E. P. & Schnitzer, M. J. In vivo brain imaging using a portable 3.9 gram two-photon fluorescence microendoscope. Opt. Lett. 30, 2272-2274 (2005).
87. Piyawattanametha, W. et al. Fast-scanning two-photon fluorescence imaging based on a microelectromechanical systems two- dimensional scanning mirror. Opt. Lett. 31, 2018-2020 (2006).
88. Sawinski, J. & Denk, W. Miniature random-access fiber scanner for in vivo multiphoton imaging. J. Appl. Phys. 102, 034701 (2007).
89. Adelsberger, H., Garaschuk, O. & Konnerth, A. Cortical calcium waves in resting newborn mice. Nature Neurosci. 8, 988-990 (2005).
90. Murayama, M., Perez-Garci, E., Luscher, H. R. & Larkum, M. E. Fiberoptic system for recording dendritic calcium signals in layer 5 neocortical pyramidal cells in freely moving rats. J. Neurophysiol. 98, 1791-1805 (2007).
91. 2+ dynamics in a cricket auditory neuron: an example of chemical computation. Science 263, 823-826 (1994).
92. Single, S. & Borst, A. Dendritic integration and its role in computing image velocity. Science 281, 1848-1850 (1998).
93. Haag, J., Denk, W. & Borst, A. Fly motion vision is based on Reichardt detectors regardless of the signal-to-noise ratio. Proc. Natl Acad. Sci. USA 101, 16333-16338 (2004).
94. Kerr, R. et al. Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans. Neuron 26, 583-594 (2000).
95. Ng, M. et al. Transmission of olfactory information between three populations of neurons in the antennal lobe of the fly. Neuron 36, 463-474 (2002).
96. Wang, J. W., Wong, A. M., Flores, J., Vosshall, L. B. & Axel, R. Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell 112, 271-282 (2003).
97. Higashijima, S., Masino, M. A., Mandel, G. & Fetcho, J. R. Imaging neuronal activity during zebrafish behavior with a genetically encoded calcium indicator. J. Neurophysiol. 90, 3986-3997 (2003).
98. 2+].
99. Tsien, R. Y. A non-disruptive technique for loading calcium buffers and indicators into cells. Nature 290, 527-528 (1981).
100. Smetters, D., Majewska, A. & Yuste, R. Detecting action potentials in neuronal populations with calcium imaging. Methods 18, 215-221 (1999).
101. Friedrich, R. W. & Korsching, S. I. Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging. Neuron 18, 737-752 (1997).
102. Friedrich, R. W. & Korsching, S. I. Chemotopic, combinatorial, and noncombinatorial odorant representations in the olfactory bulb revealed using a voltage-sensitive axon tracer. J. Neurosci. 18, 9977-9988 (1998).
103. Sato, T. R., Gray, N. W., Mainen, Z. F. & Svoboda, K. The functional microarchitecture of the mouse barrel cortex. PLoS Biol. 5, e189 (2007).
104. Sullivan, M. R., Nimmerjahn, A., Sarkisov, D. V., Helmchen, F. & Wang, S. S. In vivo calcium imaging of circuit activity in cerebellar cortex. J. Neurophysiol. 94, 1636-1644 (2005).
105. Niell, C. M. & Smith, S. J. Functional imaging reveals rapid development of visual response properties in the zebrafish tectum. Neuron 45, 941-951 (2005).
106. Wachowiak, M., Denk, W. & Friedrich, R. W. Functional organization of sensory input to the olfactory bulb glomerulus analyzed by two-photon calcium imaging. Proc. Natl Acad. Sci. USA 101, 9097-9102 (2004).
107. Li, J. et al. Early development of functional spatial maps in the zebrafish olfactory bulb. J. Neurosci. 25, 5784-5795 (2005).
108. Yaksi, E., Judkewitz, B. & Friedrich, R. W. Topological reorganization of odor representations in the olfactory bulb. PLoS Biol. 5, e178 (2007).
109. Bonhoeffer, T. & Grinvald, A. Iso-orientation domains in cat visual-cortex are arranged in pinwheel-like patterns. Nature 353, 429-431 (1991). Using intrinsic optical imaging of the cat visual cortex, this study was the first to show the existence of orientation pinwheels.
110. Brecht, M., Roth, A. & Sakmann, B. Dynamic receptive fields of reconstructed pyramidal cells in layers 3 and 2 of rat somatosensory barrel cortex. J. Physiol. 553, 243-265 (2003).
111. de Kock, C. P., Bruno, R. M., Spors, H. & Sakmann, B. Layer- and cell-type-specific suprathreshold stimulus representation in rat primary somatosensory cortex. J. Physiol. 581, 139-154 (2007).
112. Nimmerjahn, A., Kirchhoff, F., Kerr, J. N. & Helmchen, F. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nature Methods 1, 31-37 (2004).
113. 2+] transients in mitral cell dendrites of frog olfactory glomeruli. Eur. J. Neurosci. 13, 1658-1672 (2001).
114. Yuste, R. & Denk, W. Dendritic spines as basic functional units of neuronal integration. Nature 375, 682-684 (1995).
115. Denk, W., Yuste, R., Svoboda, K. & Tank, D. W. Imaging calcium dynamics in dendritic spines. Curr. Opin. Neurobiol. 6, 372-378 (1996).
116. 2+ indicator proteins in transgenic mice under TET control. PLoS Biol. 2, e163 (2004).
117. 2+ indicator protein. Eur. J. Neurosci. 22, 627-635 (2005).
118. Heim, N. et al. Improved calcium imaging in transgenic mice expressing a troponin C-based biosensor. Nature Methods 4, 127-129 (2007).
119. Diez-Garcia, J., Akemann, W. & Knopfel, T. In vivo calcium imaging from genetically specified target cells in mouse cerebellum. Neuroimage 34, 859-869 (2007).
120. Osten, P., Grinevich, V. & Cetin, A. in Conditional Mutagenesis: An Approach to Disease Models (Handbook of Experimental Pharmacology) (eds Feil, R. & Metzger, D.) 177-202 (Springer, Berlin, 2007).
121. Margrie, T. W. et al. Targeted whole-cell recordings in the mammalian brain in vivo. Neuron 39, 911-918 (2003).
122. Euler, T., Detwiler, P. B. & Denk, W. Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418, 845-852 (2002).
123. Stuart, G. J., Dodt, H. U. & Sakmann, B. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch. 423, 511-518 (1993).
124. Dittgen, T. et al. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc. Natl Acad. Sci. USA 101, 18206-18211 (2004).
125. Komai, S. et al. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development. Nature Neurosci. 9, 1125-1133 (2006).
126. Niell, C. M., Meyer, M. P. & Smith, S. J. In vivo imaging of synapse formation on a growing dendritic arbor. Nature Neurosci. 7, 254-260 (2004).
127. Calverley, R. K. & Jones, D. G. Contributions of dendritic spines and perforated synapses to synaptic plasticity. Brain Res. Brain Res. Rev. 15, 215-249 (1990).
128. Balicegordon, R. J. & Lichtman, J. W. In vivo visualization of the growth of presynaptic and postsynaptic elements of neuromuscular-junctions in the mouse. J. Neurosci. 10, 894-908 (1990).
129. Sanes, J. R. & Lichtman, J. W. Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 389-442 (1999).
130. Javaherian, A. & Cline, H. T. Coordinated motor neuron axon growth and neuromuscular synaptogenesis are promoted by CPG15 in vivo. Neuron 45, 505-512 (2005).
131. Hua, J. Y., Smear, M. C., Baier, H. & Smith, S. J. Regulation of axon growth in vivo by activity-based competition. Nature 434, 1022-1026 (2005).
132. Wu, G. Y. & Cline, H. T. Time-lapse in vivo imaging of the morphological development of Xenopus optic tectal interneurons. J. Comp. Neurol. 459, 392-406 (2003).
133. Kulesa, P. M. & Fraser, S. E. Cell dynamics during somite boundary formation revealed by time-lapse analysis. Science 298, 991-995 (2002).
134. Feng, G. et al. Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers. Neuron 25, 295-306 (2000).
135. Zuo, Y., Lin, A., Chang, P. & Gan, W. B. Development of long-term dendritic spine stability in diverse regions of cerebral cortex. Neuron 46, 181-189 (2005).
136. Holtmaat, A., Wilbrecht, L., Knott, G. W., Welker, E. & Svoboda, K. Experience-dependent and cell-type-specific spine growth in the neocortex. Nature 441, 979-983 (2006).
137. Nimmerjahn, A., Kirchhoff, F. & Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308, 1314-1318 (2005).
138. De Paola, V. et al. Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex. Neuron 49, 861-875 (2006).
139. Mizrahi, A. Dendritic development and plasticity of adult-born neurons in the mouse olfactory bulb. Nature Neurosci. 10, 444-452 (2007).
140. 3 regenerative amplifier. Opt. Lett. 28, 1022-1024 (2003).
141. Theer, P. & Denk, W. On the fundamental imaging-depth limit in two-photon microscopy. J. Opt. Soc. Am. A Opt. Image Sci. Vis. 23, 3139-3149 (2006). This paper provides a thorough description, both theoretical and experimental, of the physical properties of two-photon imaging in light scattering media, with a focus on the imaging-depth limit.
142. Feierabend, M., Ruckel, M. & Denk, W. Coherence-gated wave-front sensing in strongly scattering samples. Opt. Lett. 29, 2255-2257 (2004).
143. Rueckel, M., Mack-Bucher, J. A. & Denk, W. Adaptive wavefront correction in two-photon microscopy using coherence-gated wavefront sensing. Proc. Natl Acad. Sci. USA 103, 17137-17142 (2006). This study showed how both imaging resolution and signal size were improved by measuring beam wavefront distortions and compensating for these distortions using adaptive optics. This technology will be of great benefit to imaging in preparations in which both intact dura and skull are required.
144. Kralik, J. D. et al. Techniques for long-term multisite neuronal ensemble recordings in behaving animals. Methods 25, 121-150 (2001).
145. Mehta, A. D., Jung, J. C., Flusberg, B. A. & Schnitzer, M. J. Fiber optic in vivo imaging in the mammalian nervous system. Curr. Opin. Neurobiol. 14, 617-628 (2004).
146. Jung, J. C., Mehta, A. D., Aksay, E., Stepnoski, R. & Schnitzer, M. J. In vivo mammalian brain imaging using one- and two-photon fluorescence microendoscopy. J. Neurophysiol. 92, 3121-3133 (2004).
147. Zucker, R. S. & Regehr, W. G. Short-term synaptic plasticity. Annu. Rev. Physiol. 64, 355-405 (2002).
148. Fan, G. Y. et al. Video-rate scanning two-photon excitation fluorescence microscopy and ratio imaging with cameleons. Biophys. J. 76, 2412-2420 (1999).
149. Lechleiter, J. D., Lin, D. T. & Sieneart, I. Multi-photon laser scanning microscopy using an acoustic optical deflector. Biophys. J. 83, 2292-2299 (2002).
150. Vucinic, D. & Sejnowski, T. A compact multiphoton 3D imaging system for recording fast neuronal activity. PLoS ONE 2, e699 (2007).
151. Gobel, W., Kampa, B. M. & Helmchen, F. Imaging cellular network dynamics in three dimensions using fast 3D laser scanning. Nature Methods 4, 73-79 (2007).
152. Livet, J. et al. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450, 56-62 (2007).
153. Levene, M. J., Dombeck, D. A., Kasischke, K. A., Molloy, R. P. & Webb, W. W. In vivo multiphoton microscopy of deep brain tissue. J. Neurophysiol. 91, 1908-1912 (2004).
154. Gobel, W., Kerr, J. N., Nimmerjahn, A. & Helmchen, F. Miniaturized two-photon microscope based on a flexible coherent fiber bundle and a gradient-index lens objective. Opt. Lett. 29, 2521-2523 (2004).
155. 2+-indicator in the zebrafish tectum.
156. Takano, T. et al. Astrocyte-mediated control of cerebral blood flow. Nature Neurosci. 9, 260-267 (2006).
157. Winship, I. R., Plaa, N. & Murphy, T. H. Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J. Neurosci. 27, 6268-6272 (2007).
158. 2+ signaling and the microvasculature in experimental mice models of Alzheimer's disease. Ann. NY Acad. Sci. 1097, 40-50 (2007).
159. Zipfel, W. R. et al. Live tissue intrinsic emission microscopy using multiphoton-excited native fluorescence and second harmonic generation. Proc. Natl Acad. Sci. USA 100, 7075-7080 (2003).
160. Misgeld, T. & Kerschensteiner, M. In vivo imaging of the diseased nervous system. Nature Rev. Neurosci. 7, 449-463 (2006).
161. Kovacevic, N. et al. A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability. Cereb. Cortex 15, 639-645 (2005).
162. Gobel, W. & Helmchen, F. New angles on neuronal dendrites in vivo. J. Neurophysiol. 98, 3770-3779 (2007).