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209 Publications

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    10/24/16 | Central brain circuitry for color-vision-modulated behaviors.
    Longden KD
    Current Biology : CB. 2016 Oct 24;26(20):R981-8. doi: 10.1016/j.cub.2016.07.071

    Color is famous for not existing in the external world: our brains create the perception of color from the spatial and temporal patterns of the wavelength and intensity of light. For an intangible quality, we have detailed knowledge of its origins and consequences. Much is known about the organization and evolution of the first phases of color processing, the filtering of light in the eye and processing in the retina, and about the final phases, the roles of color in behavior and natural selection. To understand how color processing in the central brain has evolved, we need well-defined pathways or circuitry where we can gauge how color contributes to the computations involved in specific behaviors. Examples of such pathways or circuitry that are dedicated to processing color cues are rare, despite the separation of color and luminance pathways early in the visual system of many species, and despite the traditional definition of color as being independent of luminance. This minireview presents examples in which color vision contributes to behaviors dominated by other visual modalities, examples that are not part of the canon of color vision circuitry. The pathways and circuitry process a range of chromatic properties of objects and their illumination, and are taken from a variety of species. By considering how color processing complements luminance processing, rather than being independent of it, we gain an additional way to account for the diversity of color coding in the central brain, its consequences for specific behaviors and ultimately the evolution of color vision.

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    07/22/16 | Comment on "A histone acetylation switch regulates H2A.Z deposition by the SWR-C remodeling enzyme".
    Wang F, Ranjan A, Wei D, Wu C
    Science. 2016 Jul 22;353(6297):358. doi: 10.1126/science.aad5921

    Watanabe et al (Reports, 12 April 2013, p. 195) study the yeast SWR1/SWR-C complex responsible for depositing the histone variant H2A.Z by replacing nucleosomal H2A with H2A.Z. They report that reversal of H2A.Z replacement is mediated by SWR1 and related INO80 on an H2A.Z nucleosome carrying H3K56Q. Using multiple assays and reaction conditions, we find no evidence of such reversal of H2A.Z exchange.

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    Card Lab
    10/03/16 | Comparative approaches to escape.
    Peek MY, Card GM
    Current Opinion in Neurobiology. 2016 Oct 3;41:167-173. doi: 10.1016/j.conb.2016.09.012

    Neural circuits mediating visually evoked escape behaviors are promising systems in which to dissect the neural basis of behavior. Behavioral responses to predator-like looming stimuli, and their underlying neural computations, are remarkably similar across species. Recently, genetic tools have been applied in this classical paradigm, revealing novel non-cortical pathways that connect loom processing to defensive behaviors in mammals and demonstrating that loom encoding models from locusts also fit vertebrate neural responses. In both invertebrates and vertebrates, relative spike-timing in descending pathways is a mechanism for escape behavior choice. Current findings suggest that experimentally tractable systems, such as Drosophila, may be applicable models for sensorimotor processing and persistent states in higher organisms.

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    Zlatic LabCardona LabFetter LabTruman LabScientific Computing Software
    10/05/16 | Competitive disinhibition mediates behavioral choice and sequences in Drosophila.
    Jovanic T, Schneider-Mizell CM, Shao M, Masson J, Denisov G, Fetter RD, Mensh BD, Truman JW, Cardona A, Zlatic M
    Cell. 2016 Oct 5;167(3):858-70. doi: 10.1016/j.cell.2016.09.009

    Even a simple sensory stimulus can elicit distinct innate behaviors and sequences. During sensorimotor decisions, competitive interactions among neurons that promote distinct behaviors must ensure the selection and maintenance of one behavior, while suppressing others. The circuit implementation of these competitive interactions is still an open question. By combining comprehensive electron microscopy reconstruction of inhibitory interneuron networks, modeling, electrophysiology, and behavioral studies, we determined the circuit mechanisms that contribute to the Drosophila larval sensorimotor decision to startle, explore, or perform a sequence of the two in response to a mechanosensory stimulus. Together, these studies reveal that, early in sensory processing, (1) reciprocally connected feedforward inhibitory interneurons implement behavioral choice, (2) local feedback disinhibition provides positive feedback that consolidates and maintains the chosen behavior, and (3) lateral disinhibition promotes sequence transitions. The combination of these interconnected circuit motifs can implement both behavior selection and the serial organization of behaviors into a sequence.

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    06/17/16 | Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms.
    Marder E, Gutierrez G, Nusbaum MP
    Developmental Neurobiology. 2016 Jun 17:. doi: 10.1002/dneu.22410

    Electrical coupling in circuits can produce non-intuitive circuit dynamics, as seen in both experimental work from the crustacean stomatogastric ganglion and in computational models inspired by the connectivity in this preparation. Ambiguities in interpreting the results of electrophysiological recordings can arise if sets of pre- or postsynaptic neurons are electrically coupled, or if the electrical coupling exhibits some specificity (e.g. rectifying, or voltage-dependent). Even in small circuits, electrical coupling can produce parallel pathways that can allow information to travel by monosynaptic and/or polysynaptic pathways. Consequently, similar changes in circuit dynamics can arise from entirely different underlying mechanisms. When neurons are coupled both chemically and electrically, modifying the relative strengths of the two interactions provides a mechanism for flexibility in circuit outputs. This, together with neuromodulation of gap junctions and coupled neurons is important both in developing and adult circuits. This article is protected by copyright. All rights reserved.

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    06/17/16 | Complicating connectomes: Electrical coupling creates parallel pathways and degenerate circuit mechanisms.
    Marder E, Gutierrez G, Nusbaum MP
    Developmental Neurobiology. 2016 Jun 17:. doi: 10.1002/dneu.22410

    Electrical coupling in circuits can produce non-intuitive circuit dynamics, as seen in both experimental work from the crustacean stomatogastric ganglion and in computational models inspired by the connectivity in this preparation. Ambiguities in interpreting the results of electrophysiological recordings can arise if sets of pre- or postsynaptic neurons are electrically coupled, or if the electrical coupling exhibits some specificity (e.g. rectifying, or voltage-dependent). Even in small circuits, electrical coupling can produce parallel pathways that can allow information to travel by monosynaptic and/or polysynaptic pathways. Consequently, similar changes in circuit dynamics can arise from entirely different underlying mechanisms. When neurons are coupled both chemically and electrically, modifying the relative strengths of the two interactions provides a mechanism for flexibility in circuit outputs. This, together with neuromodulation of gap junctions and coupled neurons is important both in developing and adult circuits. This article is protected by copyright. All rights reserved.

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    04/18/16 | Computational Analysis of Behavior.
    Egnor SE, Branson K
    Annual Review of Neuroscience. 2016 Apr 18;39:217-36. doi: 10.1146/annurev-neuro-070815-013845

    In this review, we discuss the emerging field of computational behavioral analysis-the use of modern methods from computer science and engineering to quantitatively measure animal behavior. We discuss aspects of experiment design important to both obtaining biologically relevant behavioral data and enabling the use of machine vision and learning techniques for automation. These two goals are often in conflict. Restraining or restricting the environment of the animal can simplify automatic behavior quantification, but it can also degrade the quality or alter important aspects of behavior. To enable biologists to design experiments to obtain better behavioral measurements, and computer scientists to pinpoint fruitful directions for algorithm improvement, we review known effects of artificial manipulation of the animal on behavior. We also review machine vision and learning techniques for tracking, feature extraction, automated behavior classification, and automated behavior discovery, the assumptions they make, and the types of data they work best with. Expected final online publication date for the Annual Review of Neuroscience Volume 39 is July 08, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

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    06/01/16 | Connectome studies on Drosophila: a short perspective on a tiny brain.
    Meinertzhagen IA
    Journal of Neurogenetics. 2016 Jun;30(2):62-8. doi: 10.3109/01677063.2016.1166224

    The brain is a network of neurons, one that generates behaviour, and knowing the former is crucial to understanding the latter. Identifying the exact network of synaptic connections, or connectome, of the fly's central nervous system is now a major objective in Drosophila neurobiology, one that has been initiated in several laboratories, especially the Janelia Research Campus of the Howard Hughes Medical Institute. Progress is most advanced in the optic neuropiles of the visual system. The effort to derive a connectome from these and other neuropile regions is proceeding by various methods of electron microscopy, especially focused-ion beam milling scanning electron microscopy, and relies upon - but is to be carefully distinguished from - published light microscopic methods that reveal the projections of genetically labelled cell types. The latter reveal those neurons that come into close proximity and are therefore candidate synaptic partners. Synaptic partnerships are not in fact reliably revealed by such candidate pairs, anatomical connections often revealing unexpected pathways. Synaptic partnerships identified from ultrastructural features provide a strong heuristic basis to interpret not only functional interactions between identified neurons, but also a powerful means to predict such interactions, and suggest functional pathways not readily predicted from existing experimental evidence. The analysis of circuit function may proceed cell by cell, by examining the behavioural outcome of either interrupting or restoring function to any one element in an anatomically defined circuit, but can be foiled by degeneracy in pathway elements. Circuit information can also be used to identify and analyse circuit motifs, and their role in higher-order network properties. These attempts in Drosophila anticipate parallel attempts in other systems, notably the inner plexiform layer of the vertebrate retina, and augment the one complete connectome already available to us, that available for 30 years in the nematode Caenorhabditis elegans.

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    Kainmueller Lab
    06/27/16 | Convexity shape constraints for image segmentation.
    Royer LA, Richmond DL, Rother C, Andres B, Kainmueller D
    IEEE Conference on Computer Vision and Pattern Recognition (CVPR). 2016 Jun 27:. doi: 10.1109/CVPR.2016.50

    Segmenting an image into multiple components is a central task in computer vision. In many practical scenarios, prior knowledge about plausible components is available. Incorporating such prior knowledge into models and algorithms for image segmentation is highly desirable, yet can be non-trivial. In this work, we introduce a new approach that allows, for the first time, to constrain some or all components of a segmentation to have convex shapes. Specifically, we extend the Minimum Cost Multicut Problem by a class of constraints that enforce convexity. To solve instances of this NP-hard integer linear program to optimality, we separate the proposed constraints in the branch-and-cut loop of a state-of-the-art ILP solver. Results on photographs and micrographs demonstrate the effectiveness of the approach as well as its advantages over the state-of-the-art heuristic.

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    Grigorieff Lab
    05/16/16 | Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril.
    Schmidt A, Annamalai K, Schmidt M, Grigorieff N, Fändrich M
    Proceedings of the National Academy of Sciences of the United States of America. 2016 May 16;113(22):6200-5. doi: 10.1073/pnas.1522282113

    Amyloid fibrils are proteinaceous aggregates associated with diseases in humans and animals. The fibrils are defined by intermolecular interactions between the fibril-forming polypeptide chains, but it has so far remained difficult to reveal the assembly of the peptide subunits in a full-scale fibril. Using electron cryomicroscopy (cryo-EM), we present a reconstruction of a fibril formed from the pathogenic core of an amyloidogenic immunoglobulin (Ig) light chain. The fibril density shows a lattice-like assembly of face-to-face packed peptide dimers that corresponds to the structure of steric zippers in peptide crystals. Interpretation of the density map with a molecular model enabled us to identify the intermolecular interactions between the peptides and rationalize the hierarchical structure of the fibril based on simple chemical principles.

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