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Lee Tzumin Lab / Publications
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16 Publications

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    Spruston LabMenon Lab
    07/30/09 | Synapse distribution suggests a two-stage model of dendritic integration in CA1 pyramidal neurons.
    Katz Y, Menon V, Nicholson DA, Geinisman Y, Kath WL, Spruston N
    Neuron. 2009 Jul 30;63(2):171-7. doi: 10.1016/j.neuron.2009.06.023

    Competing models have been proposed to explain how neurons integrate the thousands of inputs distributed throughout their dendritic trees. In a simple global integration model, inputs from all locations sum in the axon. In a two-stage integration model, inputs contribute directly to dendritic spikes, and outputs from multiple branches sum in the axon. These two models yield opposite predictions of how synapses at different dendritic locations should be scaled if they are to contribute equally to neuronal output. We used serial-section electron microscopy to reconstruct individual apical oblique dendritic branches of CA1 pyramidal neurons and observe a synapse distribution consistent with the two-stage integration model. Computational modeling suggests that the observed synapse distribution enhances the contribution of each dendritic branch to neuronal output.

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    07/30/09 | Tweek, an evolutionarily conserved protein, is required for synaptic vesicle recycling.
    Verstreken P, Ohyama T, Haueter C, Habets RL, Lin YQ, Swan LE, Ly CV, Venken KJ, De Camilli P, Bellen HJ
    Neuron. 2009 Jul 30;63(2):203-15. doi: 10.1016/j.neuron.2009.06.017

    Synaptic vesicle endocytosis is critical for maintaining synaptic communication during intense stimulation. Here we describe Tweek, a conserved protein that is required for synaptic vesicle recycling. tweek mutants show reduced FM1-43 uptake, cannot maintain release during intense stimulation, and harbor larger than normal synaptic vesicles, implicating it in vesicle recycling at the synapse. Interestingly, the levels of a fluorescent PI(4,5)P(2) reporter are reduced at tweek mutant synapses, and the probe is aberrantly localized during stimulation. In addition, various endocytic adaptors known to bind PI(4,5)P(2) are mislocalized and the defects in FM1-43 dye uptake and adaptor localization are partially suppressed by removing one copy of the phosphoinositide phosphatase synaptojanin, suggesting a role for Tweek in maintaining proper phosphoinositide levels at synapses. Our data implicate Tweek in regulating synaptic vesicle recycling via an action mediated at least in part by the regulation of PI(4,5)P(2) levels or availability at the synapse.

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    Chklovskii Lab
    07/28/09 | Maximization of the connectivity repertoire as a statistical principle governing the shapes of dendritic arbors.
    Wen Q, Stepanyants A, Elston GN, Grosberg AY, Chklovskii DB
    Proceedings of the National Academy of Sciences of the United States of America. 2009 Jul 28;106(30):12536-41. doi: 10.1371/journal.pcbi.1001066

    The shapes of dendritic arbors are fascinating and important, yet the principles underlying these complex and diverse structures remain unclear. Here, we analyzed basal dendritic arbors of 2,171 pyramidal neurons sampled from mammalian brains and discovered 3 statistical properties: the dendritic arbor size scales with the total dendritic length, the spatial correlation of dendritic branches within an arbor has a universal functional form, and small parts of an arbor are self-similar. We proposed that these properties result from maximizing the repertoire of possible connectivity patterns between dendrites and surrounding axons while keeping the cost of dendrites low. We solved this optimization problem by drawing an analogy with maximization of the entropy for a given energy in statistical physics. The solution is consistent with the above observations and predicts scaling relations that can be tested experimentally. In addition, our theory explains why dendritic branches of pyramidal cells are distributed more sparsely than those of Purkinje cells. Our results represent a step toward a unifying view of the relationship between neuronal morphology and function.

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    Kainmueller Lab
    07/26/09 | 3D reconstruction of the human rib cage from 2D projection images using a statistical shape model.
    Dworzak J, Lamecker H, von Berg J, Klinder T, Lorenz C, Kainmüller D, Seim H, Hege H, Zachow S
    International journal of computer assisted radiology and surgery. 2010 Mar;5(2):111-24. doi: 10.1007/s11548-009-0390-2

    PURPOSE: This paper describes an approach for the three-dimensional (3D) shape and pose reconstruction of the human rib cage from few segmented two-dimensional (2D) projection images. Our work is aimed at supporting temporal subtraction techniques of subsequently acquired radiographs by establishing a method for the assessment of pose differences in sequences of chest radiographs of the same patient.

    METHODS: The reconstruction method is based on a 3D statistical shape model (SSM) of the rib cage, which is adapted to binary 2D projection images of an individual rib cage. To drive the adaptation we minimize a distance measure that quantifies the dissimilarities between 2D projections of the 3D SSM and the projection images of the individual rib cage. We propose different silhouette-based distance measures and evaluate their suitability for the adaptation of the SSM to the projection images.

    RESULTS: An evaluation was performed on 29 sets of biplanar binary images (posterior-anterior and lateral). Depending on the chosen distance measure, our experiments on the combined reconstruction of shape and pose of the rib cages yield reconstruction errors from 2.2 to 4.7 mm average mean 3D surface distance. Given a geometry of an individual rib cage, the rotational errors for the pose reconstruction range from 0.1 degrees to 0.9 degrees.

    CONCLUSIONS: The results show that our method is suitable for the estimation of pose differences of the human rib cage in binary projection images. Thus, it is able to provide crucial 3D information for registration during the generation of 2D subtraction images.

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    07/26/09 | Fast throughput low voltage scanning transmission electron microscope imaging of nano-resolution three dimensional tissue.
    Bolorizadeh M, Hess HF
    Microscopy and Microanalysis. 2009 Jul 26;15:642-3. doi: 10.1017/S1431927609092435
    Looger Lab
    07/26/09 | Three dimensional super resolution fluorescence imaging of single bacterial cells by stereo photoactivated localization microscopy.
    Tang J, Vaziri A, Akerboom JP, Looger L, Shank CV
    Microscopy and Microanalysis. 2009 July 26;15:564-5. doi: 10.1017/S1431927609095737
    07/26/09 | Three-dimensional super-resolution imaging of thick biological samples.
    Vaziri A, Tang J, Shroff H, Shank C
    Microscopy and Microanalysis. 2009 Jul 26;15:36-7. doi: 10.1017/S1431927609092368
    07/24/09 | Drosophila, a genetic model system to study cocaine-related behaviors: a review with focus on LIM-only proteins.
    Heberlein U, Tsai LT, Kapfhamer D, Lasek AW
    Neuropharmacology. 2009;56 Suppl 1:97-106. doi: 10.1016/j.neuropharm.2008.07.023

    In the last decade, the fruit fly Drosophila melanogaster, highly accessible to genetic, behavioral and molecular analyses, has been introduced as a novel model organism to help decipher the complex genetic, neurochemical, and neuroanatomical underpinnings of behaviors induced by drugs of abuse. Here we review these data, focusing specifically on cocaine-related behaviors. Several of cocaine's most characteristic properties have been recapitulated in Drosophila. First, cocaine induces motor behaviors in flies that are remarkably similar to those observed in mammals. Second, repeated cocaine administration induces behavioral sensitization a form of behavioral plasticity believed to underlie certain aspects of addiction. Third, a key role for dopaminergic systems in mediating cocaine's effects has been demonstrated through both pharmacological and genetic methods. Finally, and most importantly, unbiased genetic screens, feasible because of the simplicity and scale with which flies can be manipulated in the laboratory, have identified several novel genes and pathways whose role in cocaine behaviors had not been anticipated. Many of these genes and pathways have been validated in mammalian models of drug addiction. We focus in this review on the role of LIM-only proteins in cocaine-induced behaviors.

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    Kainmueller Lab
    07/20/09 | Multi-object segmentation of head bones.
    Kainmueller D, Lamecker H, Seim H, Zachow S
    MIDAS Journal. 2009 Jul 20:

    We present a fully automatic method for 3D segmentation of the mandibular bone from CT data. The method includes an adaptation of statistical shape models of the mandible, the skull base and the midfacial bones, followed by a simultaneous graph-based optimization of adjacent deformable models. The adaptation of the models to the image data is performed according to a heuristic model of the typical intensity distribution in the vincinity of the bone boundary, with special focus on an accurate discrimination of adjacent bones in joint regions. An evaluation of our method based on 18 CT scans shows that a manual correction of the automatic segmentations is not necessary in approx. 60% of the axial slices that contain the mandible.

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    07/20/09 | Simplified approach to diffraction tomography in optical microscopy.
    Fiolka R, Wicker K, Heintzmann R, Stemmer A
    Optics Express. 2009 Jul 20;17(15):12407-17

    We present a novel microscopy technique to measure the scattered wavefront emitted from an optically transparent microscopic object. The complex amplitude is decoded via phase stepping in a common-path interferometer, enabling high mechanical stability. We demonstrate theoretically and practically that the incoherent summation of multiple illumination directions into a single image increases the resolving power and facilitates image reconstruction in diffraction tomography. We propose a slice-by-slice object-scatter extraction algorithm entirely based in real space in combination with ordinary z-stepping. Thereby the computational complexity affiliated with tomographic methods is significantly reduced. Using the first order Born approximation for weakly scattering objects it is possible to obtain estimates of the scattering density from the exitwaves.

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