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5 Publications

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    Cardona LabFunke Lab
    11/18/15 | Who is talking to whom: Synaptic partner detection in anisotropic volumes of insect brain.
    Kreshuk A, Funke J, Cardona A, Hamprecht FA
    Medical Image Computing and Computer-Assisted Intervention -- MICCAI 2015:661-8. doi: 10.1007/978-3-319-24553-9_81

    Automated reconstruction of neural connectivity graphs from electron microscopy image stacks is an essential step towards large-scale neural circuit mapping. While significant progress has recently been made in automated segmentation of neurons and detection of synapses, the problem of synaptic partner assignment for polyadic (one-to-many) synapses, prevalent in the Drosophila brain, remains unsolved. In this contribution, we propose a method which automatically assigns pre- and postsynaptic roles to neurites adjacent to a synaptic site. The method constructs a probabilistic graphical model over potential synaptic partner pairs which includes factors to account for a high rate of one-to-many connections, as well as the possibility of the same neuron to be pre-synaptic in one synapse and post-synaptic in another. The algorithm has been validated on a publicly available stack of ssTEM images of Drosophila neural tissue and has been shown to reconstruct most of the synaptic relations correctly.

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    Turaga LabCardona Lab
    11/05/15 | Crowdsourcing the creation of image segmentation algorithms for connectomics.
    Arganda-Carreras I, Turaga SC, Berger DR, Ciresan D, Giusti A, Gambardella LM, Schmidhuber J, Laptev D, Dwivedi S, Buhmann JM
    Frontiers in Neuroanatomy. 2015 Nov 05;9:142. doi: 10.3389/fnana.2015.00142

    To stimulate progress in automating the reconstruction of neural circuits, we organized the first international challenge on 2D segmentation of electron microscopic (EM) images of the brain. Participants submitted boundary maps predicted for a test set of images, and were scored based on their agreement with a consensus of human expert annotations. The winning team had no prior experience with EM images, and employed a convolutional network. This “deep learning” approach has since become accepted as a standard for segmentation of EM images. The challenge has continued to accept submissions, and the best so far has resulted from cooperation between two teams. The challenge has probably saturated, as algorithms cannot progress beyond limits set by ambiguities inherent in 2D scoring and the size of the test dataset. Retrospective evaluation of the challenge scoring system reveals that it was not sufficiently robust to variations in the widths of neurite borders. We propose a solution to this problem, which should be useful for a future 3D segmentation challenge.

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    Cardona LabTruman LabFetter Lab
    10/21/15 | Even-Skipped(+) interneurons are core components of a sensorimotor circuit that maintains left-right symmetric muscle contraction amplitude.
    Heckscher ES, Zarin AA, Faumont S, Clark MQ, Manning L, Fushiki A, Schneider-Mizell CM, Fetter RD, Truman JW, Zwart MF, Landgraf M, Cardona A, Lockery SR, Doe CQ
    Neuron. 2015 Oct 21;88(2):314-29. doi: 10.1016/j.neuron.2015.09.009

    Bilaterally symmetric motor patterns-those in which left-right pairs of muscles contract synchronously and with equal amplitude (such as breathing, smiling, whisking, and locomotion)-are widespread throughout the animal kingdom. Yet, surprisingly little is known about the underlying neural circuits. We performed a thermogenetic screen to identify neurons required for bilaterally symmetric locomotion in Drosophila larvae and identified the evolutionarily conserved Even-skipped(+) interneurons (Eve/Evx). Activation or ablation of Eve(+) interneurons disrupted bilaterally symmetric muscle contraction amplitude, without affecting the timing of motor output. Eve(+) interneurons are not rhythmically active and thus function independently of the locomotor CPG. GCaMP6 calcium imaging of Eve(+) interneurons in freely moving larvae showed left-right asymmetric activation that correlated with larval behavior. TEM reconstruction of Eve(+) interneuron inputs and outputs showed that the Eve(+) interneurons are at the core of a sensorimotor circuit capable of detecting and modifying body wall muscle contraction.

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    Zlatic LabFetter LabBranson LabSimpson LabTruman LabCardona Lab
    04/20/15 | A multilevel multimodal circuit enhances action selection in Drosophila.
    Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JV, Franconville R, Rivera-Alba M, Mensh BD, Branson KM, Simpson JH, Truman JW, Cardona A, Zlatic M
    Nature. 2015 Apr 20;520(7549):633-9. doi: 10.1038/nature14297

    Natural events present multiple types of sensory cues, each detected by a specialized sensory modality. Combining information from several modalities is essential for the selection of appropriate actions. Key to understanding multimodal computations is determining the structural patterns of multimodal convergence and how these patterns contribute to behaviour. Modalities could converge early, late or at multiple levels in the sensory processing hierarchy. Here we show that combining mechanosensory and nociceptive cues synergistically enhances the selection of the fastest mode of escape locomotion in Drosophila larvae. In an electron microscopy volume that spans the entire insect nervous system, we reconstructed the multisensory circuit supporting the synergy, spanning multiple levels of the sensory processing hierarchy. The wiring diagram revealed a complex multilevel multimodal convergence architecture. Using behavioural and physiological studies, we identified functionally connected circuit nodes that trigger the fastest locomotor mode, and others that facilitate it, and we provide evidence that multiple levels of multimodal integration contribute to escape mode selection. We propose that the multilevel multimodal convergence architecture may be a general feature of multisensory circuits enabling complex input–output functions and selective tuning to ecologically relevant combinations of cues.

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    Cardona LabZlatic Lab
    01/13/15 | Sensory determinants of behavioral dynamics in Drosophila thermotaxis.
    Klein M, Afonso B, Vonner AJ, Hernandez-Nunez L, Berck M, Tabone CJ, Kane EA, Pieribone VA, Nitabach MN, Cardona A, Zlatic M, Sprecher SG, Gershow M, Garrity PA, Samuel AD
    Proceedings of the National Academy of Sciences of the United States of America. 2015 Jan 13;112(2):E220-9. doi: 10.1073/pnas.1416212112

    Complex animal behaviors are built from dynamical relationships between sensory inputs, neuronal activity, and motor outputs in patterns with strategic value. Connecting these patterns illuminates how nervous systems compute behavior. Here, we study Drosophila larva navigation up temperature gradients toward preferred temperatures (positive thermotaxis). By tracking the movements of animals responding to fixed spatial temperature gradients or random temperature fluctuations, we calculate the sensitivity and dynamics of the conversion of thermosensory inputs into motor responses. We discover three thermosensory neurons in each dorsal organ ganglion (DOG) that are required for positive thermotaxis. Random optogenetic stimulation of the DOG thermosensory neurons evokes behavioral patterns that mimic the response to temperature variations. In vivo calcium and voltage imaging reveals that the DOG thermosensory neurons exhibit activity patterns with sensitivity and dynamics matched to the behavioral response. Temporal processing of temperature variations carried out by the DOG thermosensory neurons emerges in distinct motor responses during thermotaxis.

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