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1404 Publications

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    12/07/16 | Inhibitory control of correlated intrinsic variability in cortical networks.
    Stringer C, Pachitariu M, Steinmetz NA, Okun M, Bartho P, Harris KD, Sahani M, Lesica NA
    eLife. 2016 Dec 07;5:. doi: 10.7554/eLife.19695

    Cortical networks exhibit intrinsic dynamics that drive coordinated, large-scale fluctuations across neuronal populations and create noise correlations that impact sensory coding. To investigate the network-level mechanisms that underlie these dynamics, we developed novel computational techniques to fit a deterministic spiking network model directly to multi-neuron recordings from different rodent species, sensory modalities, and behavioral states. The model generated correlated variability without external noise and accurately reproduced the diverse activity patterns in our recordings. Analysis of the model parameters suggested that differences in noise correlations across recordings were due primarily to differences in the strength of feedback inhibition. Further analysis of our recordings confirmed that putative inhibitory neurons were indeed more active during desynchronized cortical states with weak noise correlations. Our results demonstrate that network models with intrinsically-generated variability can accurately reproduce the activity patterns observed in multi-neuron recordings and suggest that inhibition modulates the interactions between intrinsic dynamics and sensory inputs to control the strength of noise correlations.

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    12/05/16 | Fast and accurate spike sorting of high-channel count probes with KiloSort.
    Pachitariu M, Steinmetz NA, Kadir SN, Carandini M, Harris KD
    Neural Information Processing Systems (NIPS 2016). 2016 Dec 05:

    New silicon technology is enabling large-scale electrophysiological recordings in vivo from hundreds to thousands of channels. Interpreting these recordings requires scalable and accurate automated methods for spike sorting, which should minimize the time required for manual curation of the results. Here we introduce KiloSort, a new integrated spike sorting framework that uses template matching both during spike detection and during spike clustering. KiloSort models the electrical voltage as a sum of template waveforms triggered on the spike times, which allows overlapping spikes to be identified and resolved. Unlike previous algorithms that compress the data with PCA, KiloSort operates on the raw data which allows it to construct a more accurate model of the waveforms. Processing times are faster than in previous algorithms thanks to batch-based optimization on GPUs. We compare KiloSort to an established algorithm and show favorable performance, at much reduced processing times. A novel post-clustering merging step based on the continuity of the templates further reduced substantially the number of manual operations required on this data, for the neurons with near-zero error rates, paving the way for fully automated spike sorting of multichannel electrode recordings.

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    12/02/16 | Inhibitory control of correlated intrinsic variability in cortical networks
    Stringer C, Pachitariu M, Steinmetz NA, Okun M, Bartho P, Harris KD, Sahani M, Lesica NA
    Elife. 12/2016;5:e19695. doi: https://doi.org/10.7554/eLife.19695

    Cortical networks exhibit intrinsic dynamics that drive coordinated, large-scale fluctuations across neuronal populations and create noise correlations that impact sensory coding. To investigate the network-level mechanisms that underlie these dynamics, we developed novel computational techniques to fit a deterministic spiking network model directly to multi-neuron recordings from different rodent species, sensory modalities, and behavioral states. The model generated correlated variability without external noise and accurately reproduced the diverse activity patterns in our recordings. Analysis of the model parameters suggested that differences in noise correlations across recordings were due primarily to differences in the strength of feedback inhibition. Further analysis of our recordings confirmed that putative inhibitory neurons were indeed more active during desynchronized cortical states with weak noise correlations. Our results demonstrate that network models with intrinsically-generated variability can accurately reproduce the activity patterns observed in multi-neuron recordings and suggest that inhibition modulates the interactions between intrinsic dynamics and sensory inputs to control the strength of noise correlations.

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    11/03/16 | From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.
    Naumann EA, Fitzgerald JE, Dunn TW, Rihel J, Sompolinsky H, Engert F
    Cell. 2016 11 03;167(4):947-960.e20. doi: 10.1016/j.cell.2016.10.019

    Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data.

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    11/02/16 | A Defensive Kicking Behavior in Response to Mechanical Stimuli Mediated by Drosophila Wing Margin Bristles.
    Li J, Zhang W, Guo Z, Wu S, Jan LY, Jan Y
    J Neurosci. 11/2016;36(44):11275-11282. doi: 10.1523/JNEUROSCI.1416-16.2016

    Mechanosensation, one of the fastest sensory modalities, mediates diverse behaviors including those pertinent for survival. It is important to understand how mechanical stimuli trigger defensive behaviors. Here, we report that Drosophila melanogaster adult flies exhibit a kicking response against invading parasitic mites over their wing margin with ultrafast speed and high spatial precision. Mechanical stimuli that mimic the mites' movement evoke a similar kicking behavior. Further, we identified a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle that forms an array along the wing margin as being essential sensory components for this behavior. Our electrophysiological recordings demonstrated that the mechanosensitivity of recurved bristles requires Nanchung and Nanchung-expressing neurons. Together, our results reveal a novel neural mechanism for innate defensive behavior through mechanosensation.

    SIGNIFICANCE STATEMENT: We discovered a previously unknown function for recurved bristles on the Drosophila melanogaster wing. We found that when a mite (a parasitic pest for Drosophila) touches the wing margin, the fly initiates a swift and accurate kick to remove the mite. The fly head is dispensable for this behavior. Furthermore, we found that a TRPV channel, Nanchung, and a specific Nanchung-expressing neuron under each recurved bristle are essential for its mechanosensitivity and the kicking behavior. In addition, touching different regions of the wing margin elicits kicking directed precisely at the stimulated region. Our experiments suggest that recurved bristles allow the fly to sense the presence of objects by touch to initiate a defensive behavior (perhaps analogous to touch-evoked scratching; Akiyama et al., 2012).

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    Kainmueller Lab
    09/19/16 | Mapping auto-context decision forests to deep ConvNets for semantic segmentation.
    Richmond DL, Kainmueller D, Yang MY, Myers EW, Rother C
    British Machine Vision Conference. 2016 Sep 19:

    In this paper, we propose a mapping from the Auto-context model to a deep Convolutional Neural Network (ConvNet), bridging the gap be- tween these two models, and helping address the challenge of training ConvNets with limited training data. 

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    07/04/16 | Protein-retention expansion microscopy of cells and tissues labeled using standard fluorescent proteins and antibodies.
    Tillberg P, Chen F, Piatkevich KD, Zhao Y, Yu CJ, English BP, Gao L, Martorell A, Suk H, Yoshida F, DeGennaro EM, Roossien DH, Gong G, Seneviratne U, Tannenbaum SR, Desimone R, Cai D, Boyden ES
    Nature Biotechnology. 2016 Jul 4;34(9):987-92. doi: 10.1038/nbt.3625

    Expansion microscopy (ExM) enables imaging of preserved specimens with nanoscale precision on diffraction-limited instead of specialized super-resolution microscopes. ExM works by physically separating fluorescent probes after anchoring them to a swellable gel. The first ExM method did not result in the retention of native proteins in the gel and relied on custom-made reagents that are not widely available. Here we describe protein retention ExM (proExM), a variant of ExM in which proteins are anchored to the swellable gel, allowing the use of conventional fluorescently labeled antibodies and streptavidin, and fluorescent proteins. We validated and demonstrated the utility of proExM for multicolor super-resolution (∼70 nm) imaging of cells and mammalian tissues on conventional microscopes.

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    06/28/16 | Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion.
    Guo Y, Wang Y, Zhang W, Meltzer S, Zanini D, Yu Y, Li J, Cheng T, Guo Z, Wang Q, Jacobs JS, Sharma Y, Eberl DF, Göpfert MC, Jan LY, Jan YN, Wang Z
    Proc Natl Acad Sci U S A. 06/2016;113(26):7243-8. doi: 10.1073/pnas.1606537113

    Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC's roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.

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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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    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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