New angles on neuronal dendrites in vivo.

Imaging technologies are well suited to study neuronal dendrites, which are key elements for synaptic integration in the CNS. Dendrites are, however, frequently oriented perpendicular to tissue surfaces, impeding in vivo imaging approaches. Here we introduce novel laser-scanning modes for two-photon microscopy that enable in vivo imaging of spatiotemporal activity patterns in dendrites. First, we developed a method to image planes arbitrarily oriented in 3D, which proved particularly beneficial for calcium imaging of parallel fibers and Purkinje cell dendrites in rat cerebellar cortex. Second, we applied free linescans -- either through multiple dendrites or along a single vertically oriented dendrite -- to reveal fast dendritic calcium dynamics in neocortical pyramidal neurons. Finally, we invented a ribbon-type 3D scanning method for imaging user-defined convoluted planes enabling simultaneous measurements of calcium signals along multiple apical dendrites. These novel scanning modes will facilitate optical probing of dendritic function in vivo.

[1]  R Llinás,et al.  Interaction experiments on the responses evoked in Purkinje cells by climbing fibres , 1966, The Journal of physiology.

[2]  R. Llinás,et al.  Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices. , 1980, The Journal of physiology.

[3]  R Y Tsien,et al.  Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator , 1982, The Journal of cell biology.

[4]  A. Aertsen,et al.  Representation of cooperative firing activity among simultaneously recorded neurons. , 1985, Journal of neurophysiology.

[5]  W. N. Ross,et al.  Mapping calcium transients in the dendrites of Purkinje cells from the guinea‐pig cerebellum in vitro. , 1987, The Journal of physiology.

[6]  Anil K. Jain,et al.  Algorithms for Clustering Data , 1988 .

[7]  W. Denk,et al.  Two-photon laser scanning fluorescence microscopy. , 1990, Science.

[8]  W. N. Ross,et al.  Calcium transients evoked by climbing fiber and parallel fiber synaptic inputs in guinea pig cerebellar Purkinje neurons. , 1992, Journal of neurophysiology.

[9]  J. Rawson,et al.  Morphology of parallel fibres in the cerebellar cortex of the rat: An experimental light and electron microscopic study with biocytin , 1994, The Journal of comparative neurology.

[10]  D. Tank,et al.  Dendritic Integration in Mammalian Neurons, a Century after Cajal , 1996, Neuron.

[11]  W. T. Thach,et al.  No clock signal in the discharge of neurons in the deep cerebellar nuclei. , 1997, Journal of neurophysiology.

[12]  D. Kleinfeld,et al.  In vivo dendritic calcium dynamics in neocortical pyramidal neurons , 1997, Nature.

[13]  D. Kleinfeld,et al.  Fluctuations and stimulus-induced changes in blood flow observed in individual capillaries in layers 2 through 4 of rat neocortex. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Llinás,et al.  Patterns of Spontaneous Purkinje Cell Complex Spike Activity in the Awake Rat , 1999, The Journal of Neuroscience.

[15]  G. Church,et al.  Systematic determination of genetic network architecture , 1999, Nature Genetics.

[16]  I. Parker,et al.  Construction of a confocal microscope for real-time x-y and x-z imaging. , 1999, Cell calcium.

[17]  I. Parker,et al.  Radial Localization of Inositol 1,4,5-Trisphosphate–sensitive Ca2+ Release Sites in Xenopus Oocytes Resolved by Axial Confocal Linescan Imaging , 1999, The Journal of general physiology.

[18]  Winfried Denk,et al.  Spread of dendritic excitation in layer 2/3 pyramidal neurons in rat barrel cortex in vivo , 1999, Nature Neuroscience.

[19]  D. Tank,et al.  In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons , 1999, Nature Neuroscience.

[20]  J. Voogd,et al.  Organization of projections from the inferior olive to the cerebellar nuclei in the rat , 2000, The Journal of comparative neurology.

[21]  N. Spruston,et al.  Diversity and dynamics of dendritic signaling. , 2000, Science.

[22]  G. Augustine,et al.  Quantification of spread of cerebellar long-term depression with chemical two-photon uncaging of glutamate. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Rafael Yuste,et al.  From form to function: calcium compartmentalization in dendritic spines , 2000, Nature Neuroscience.

[24]  R. Llinás,et al.  The isochronic band hypothesis and climbing fibre regulation of motricity: an experimental study , 2001, The European journal of neuroscience.

[25]  J Mertz,et al.  Odor-evoked calcium signals in dendrites of rat mitral cells. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[26]  I. Parker,et al.  Construction of a two-photon microscope for video-rate Ca(2+) imaging. , 2001, Cell calcium.

[27]  Y Shinoda,et al.  The Entire Trajectories of Single Olivocerebellar Axons in the Cerebellar Cortex and their Contribution to Cerebellar Compartmentalization , 2001, The Journal of Neuroscience.

[28]  Jack Waters,et al.  Ca2+ imaging in the mammalian brain in vivo. , 2002, European journal of pharmacology.

[29]  Ujjwal Maulik,et al.  Performance Evaluation of Some Clustering Algorithms and Validity Indices , 2002, IEEE Trans. Pattern Anal. Mach. Intell..

[30]  Patricia De la Vega,et al.  Discovery of Gene Function by Expression Profiling of the Malaria Parasite Life Cycle , 2003, Science.

[31]  W. Webb,et al.  Nonlinear magic: multiphoton microscopy in the biosciences , 2003, Nature Biotechnology.

[32]  C. Stosiek,et al.  In vivo two-photon calcium imaging of neuronal networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Sandrine Dudoit,et al.  Bagging to Improve the Accuracy of A Clustering Procedure , 2003, Bioinform..

[34]  Adil M. Bagirov,et al.  New algorithms for multi-class cancer diagnosis using tumor gene expression signatures , 2003, Bioinform..

[35]  E. Audinat,et al.  Action Potential Propagation in Dendrites of Rat Mitral Cells In Vivo , 2003, The Journal of Neuroscience.

[36]  Bert Sakmann,et al.  Supralinear Ca2+ Influx into Dendritic Tufts of Layer 2/3 Neocortical Pyramidal Neurons In Vitro and In Vivo , 2003, The Journal of Neuroscience.

[37]  F. Helmchen,et al.  Boosting of Action Potential Backpropagation by Neocortical Network Activity In Vivo , 2004, The Journal of Neuroscience.

[38]  Takeharu Nagai,et al.  Functional Fluorescent Ca2+ Indicator Proteins in Transgenic Mice under TET Control , 2004, PLoS biology.

[39]  Bartlett W. Mel,et al.  Computational subunits in thin dendrites of pyramidal cells , 2004, Nature Neuroscience.

[40]  Patrik D'haeseleer,et al.  How does gene expression clustering work? , 2005, Nature Biotechnology.

[41]  Atsushi Miyawaki,et al.  Innovations in the Imaging of Brain Functions using Fluorescent Proteins , 2005, Neuron.

[42]  B. Kampa,et al.  Synaptic integration in dendritic trees. , 2005, Journal of neurobiology.

[43]  Jonathan D Victor,et al.  Spike train metrics , 2005, Current Opinion in Neurobiology.

[44]  Sooyoung Chung,et al.  Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex , 2005, Nature.

[45]  H. Sompolinsky,et al.  Bistability of cerebellar Purkinje cells modulated by sensory stimulation , 2005, Nature Neuroscience.

[46]  David S. Greenberg,et al.  Imaging input and output of neocortical networks in vivo. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[47]  W. Denk,et al.  Deep tissue two-photon microscopy , 2005, Nature Methods.

[48]  Shigeo Watanabe,et al.  Synaptically Activated Ca2+ Release From Internal Stores in CNS Neurons , 2005, Cellular and Molecular Neurobiology.

[49]  S. Wang,et al.  In vivo calcium imaging of circuit activity in cerebellar cortex. , 2005, Journal of neurophysiology.

[50]  P. Saggau,et al.  Fast three-dimensional laser scanning scheme using acousto-optic deflectors. , 2005, Journal of biomedical optics.

[51]  A. Konnerth,et al.  Determinants of postsynaptic Ca2+ signaling in Purkinje neurons. , 2005, Cell calcium.

[52]  Shy Shoham,et al.  Rapid neurotransmitter uncaging in spatially defined patterns , 2005, Nature Methods.

[53]  Rafael Kurtz,et al.  Application of multiline two-photon microscopy to functional in vivo imaging , 2006, Journal of Neuroscience Methods.

[54]  P. Saggau,et al.  Random-access Multiphoton (ramp) Microscopy Fast Functional Imaging of Single Neurons Using , 2005 .

[55]  Knut Holthoff,et al.  Dendritic spikes and activity-dependent synaptic plasticity , 2006, Cell and Tissue Research.

[56]  J. Eggermont.  Properties of correlated neural activity clusters in cat auditory cortex resemble those of neural assemblies. , 2006, Journal of neurophysiology.

[57]  E. Yaksi,et al.  Reconstruction of firing rate changes across neuronal populations by temporally deconvolved Ca2+ imaging , 2006, Nature Methods.

[58]  George L. Gerstein,et al.  Two enhancements of the gravity algorithm for multiple spike train analysis , 2006, Journal of Neuroscience Methods.

[59]  J. Léger,et al.  Ultrafast random-access scanning in two-photon microscopy using acousto-optic deflectors , 2006, Journal of Neuroscience Methods.

[60]  David S. Greenberg,et al.  Spatial Organization of Neuronal Population Responses in Layer 2/3 of Rat Barrel Cortex , 2007, The Journal of Neuroscience.

[61]  Oliver Griesbeck,et al.  Improved calcium imaging in transgenic mice expressing a troponin C–based biosensor , 2007, Nature Methods.

[62]  Pál Maák,et al.  Random access three-dimensional two-photon microscopy. , 2007, Applied optics.

[63]  F. Helmchen,et al.  Calcium indicator loading of neurons using single-cell electroporation , 2007, Pflügers Archiv - European Journal of Physiology.

[64]  Shin Nagayama,et al.  In Vivo Simultaneous Tracing and Ca2+ Imaging of Local Neuronal Circuits , 2007, Neuron.

[65]  Benjamin R. Arenkiel,et al.  In Vivo Light-Induced Activation of Neural Circuitry in Transgenic Mice Expressing Channelrhodopsin-2 , 2007, Neuron.

[66]  D. Tank,et al.  Imaging Large-Scale Neural Activity with Cellular Resolution in Awake, Mobile Mice , 2007, Neuron.

[67]  F. Helmchen,et al.  Innovative Methodology New Angles on Neuronal Dendrites In Vivo , 2007 .

[68]  F. Helmchen,et al.  Imaging cellular network dynamics in three dimensions using fast 3D laser scanning , 2007, Nature Methods.

[69]  Thomas Knöpfel,et al.  In vivo calcium imaging from genetically specified target cells in mouse cerebellum , 2007, NeuroImage.

[70]  Feng Zhang,et al.  Multimodal fast optical interrogation of neural circuitry , 2007, Nature.

[71]  Jonathan D. Victor,et al.  Dynamic programming algorithms for comparing multineuronal spike trains via cost-based metrics and alignments , 2007, Journal of Neuroscience Methods.

[72]  Automated sorting of intracellular calcium signals for large-scale imaging studies of neuronal and glial populations , 2008 .

[73]  Heng Tao Shen,et al.  Principal Component Analysis , 2009, Encyclopedia of Biometrics.