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23 Publications

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    Menon Lab
    07/16/14 | A high-resolution spatiotemporal atlas of gene expression of the developing mouse brain.
    Thompson CL, Ng L, Menon V, Martinez S, Lee C, Glattfelder K, Sunkin SM, Henry A, Lau C, Dang C, Garcia-Lopez R, Martinez-Ferre A, Pombero A, Rubenstein JL, Wakeman WB, Hohmann J, Dee N, Sodt AJ, Young R, Smith K, Nguyen T, Kidney J, Kuan L, Jeromin A, Kaykas A, Miller J, Page D, Orta G, Bernard A, Riley Z, Smith S, Wohnoutka P, Hawrylycz MJ, Puelles L, Jones AR
    Neuron. 2014 Jul 16;83(2):309-23. doi: 10.1016/j.neuron.2014.05.033

    To provide a temporal framework for the genoarchitecture of brain development, we generated in situ hybridization data for embryonic and postnatal mouse brain at seven developmental stages for ∼2,100 genes, which were processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, seven reference atlases, an ontogenetic ontology, and tools to explore coexpression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified. A temporal shift in the principles governing the molecular organization of the brain was detected, with transient neuromeric, plate-based organization of the brain present at E11.5 and E13.5. Finally, these data provided a transcription factor code that discriminates brain structures and identifies the developmental age of a tissue, providing a foundation for eventual genetic manipulation or tracking of specific brain structures over development. The resource is available as the Allen Developing Mouse Brain Atlas (http://developingmouse.brain-map.org).

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    Cui Lab
    07/29/14 | A self-adaptive method for creating high efficiency communication channels through random scattering media.
    Hao X, Martin-Rouault L, Cui M
    Science Reports. 2014 Jul 29;4:5874. doi: 10.1038/srep05874

    Controlling the propagation of electromagnetic waves is important to a broad range of applications. Recent advances in controlling wave propagation in random scattering media have enabled optical focusing and imaging inside random scattering media. In this work, we propose and demonstrate a new method to deliver optical power more efficiently through scattering media. Drastically different from the random matrix characterization approach, our method can rapidly establish high efficiency communication channels using just a few measurements, regardless of the number of optical modes, and provides a practical and robust solution to boost the signal levels in optical or short wave communications. We experimentally demonstrated analog and digital signal transmission through highly scattering media with greatly improved performance. Besides scattering, our method can also reduce the loss of signal due to absorption. Experimentally, we observed that our method forced light to go around absorbers, leading to even higher signal improvement than in the case of purely scattering media. Interestingly, the resulting signal improvement is highly directional, which provides a new means against eavesdropping.

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    Card LabLeonardo Lab
    07/17/14 | A spike-timing mechanism for action selection.
    von Reyn CR, Breads P, Peek MY, Zheng GZ, Williamson WR, Yee AL, Leonardo A, Card GM
    Nature Neuroscience. 2014 Jul 17;17(7):962-70. doi: 10.1038/nn.3741

    We discovered a bimodal behavior in the genetically tractable organism Drosophila melanogaster that allowed us to directly probe the neural mechanisms of an action selection process. When confronted by a predator-mimicking looming stimulus, a fly responds with either a long-duration escape behavior sequence that initiates stable flight or a distinct, short-duration sequence that sacrifices flight stability for speed. Intracellular recording of the descending giant fiber (GF) interneuron during head-fixed escape revealed that GF spike timing relative to parallel circuits for escape actions determined which of the two behavioral responses was elicited. The process was well described by a simple model in which the GF circuit has a higher activation threshold than the parallel circuits, but can override ongoing behavior to force a short takeoff. Our findings suggest a neural mechanism for action selection in which relative activation timing of parallel circuits creates the appropriate motor output.

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    07/21/14 | Abdominal-B neurons control Drosophila virgin female receptivity.
    Bussell JJ, Yapici N, Zhang SX, Dickson BJ, Vosshall LB
    Current Biology. 2014 Jul 21;24(14):1584-95. doi: 10.1016/j.cub.2014.06.011

    BACKGROUND: Female sexual receptivity offers an excellent model for complex behavioral decisions. The female must parse her own reproductive state, the external environment, and male sensory cues to decide whether to copulate. In the fly Drosophila melanogaster, virgin female receptivity has received relatively little attention, and its neural circuitry and individual behavioral components remain unmapped. Using a genome-wide neuronal RNAi screen, we identify a subpopulation of neurons responsible for pausing, a novel behavioral aspect of virgin female receptivity characterized in this study.

    RESULTS: We show that Abdominal-B (Abd-B), a homeobox transcription factor, is required in developing neurons for high levels of virgin female receptivity. Silencing adult Abd-B neurons significantly decreased receptivity. We characterize two components of receptivity that are elicited in sexually mature females by male courtship: pausing and vaginal plate opening. Silencing Abd-B neurons decreased pausing but did not affect vaginal plate opening, demonstrating that these two components of female sexual behavior are functionally separable. Synthetic activation of Abd-B neurons increased pausing, but male courtship song alone was not sufficient to elicit this behavior.

    CONCLUSIONS: Our results provide an entry point to the neural circuit controlling virgin female receptivity. The female integrates multiple sensory cues from the male to execute discrete motor programs prior to copulation. Abd-B neurons control pausing, a key aspect of female sexual receptivity, in response to male courtship.

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    07/16/14 | Accessing the third dimension in localization-based super-resolution microscopy.
    Hajj B, El Beheiry M, Izeddin I, Darzacq X, Dahan M
    Physical Chemistry Chemical Physics. 2014 Jul 16;16(31):16340-8. doi: 10.1039/c4cp01380h

    Only a few years after its inception, localization-based super-resolution microscopy has become widely employed in biological studies. Yet, it is primarily used in two-dimensional imaging and accessing the organization of cellular structures at the nanoscale in three dimensions (3D) still poses important challenges. Here, we review optical and computational techniques that enable the 3D localization of individual emitters and the reconstruction of 3D super-resolution images. These techniques are grouped into three main categories: PSF engineering, multiple plane imaging and interferometric approaches. We provide an overview of their technical implementation as well as commentary on their applicability. Finally, we discuss future trends in 3D localization-based super-resolution microscopy.

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    07/02/14 | Ascending SAG neurons control sexual receptivity of Drosophila females.
    Feng K, Palfreyman MT, Häsemeyer M, Talsma A, Dickson BJ
    Neuron. 2014 Jul 2;83(1):135-48. doi: 10.1016/j.neuron.2014.05.017

    Mating induces pronounced changes in female reproductive behavior, typically including a dramatic reduction in sexual receptivity. In Drosophila, postmating behavioral changes are triggered by sex peptide (SP), a male seminal fluid peptide that acts via a receptor (SPR) expressed in sensory neurons (SPSNs) of the female reproductive tract. Here, we identify second-order neurons that mediate the behavioral changes induced by SP. These SAG neurons receive synaptic input from SPSNs in the abdominal ganglion and project to the dorsal protocerebrum. Silencing SAG neurons renders virgin females unreceptive, whereas activating them increases the receptivity of females that have already mated. Physiological experiments demonstrate that SP downregulates the excitability of the SPSNs, and hence their input onto SAG neurons. These data thus provide a physiological correlate of mating status in the female central nervous system and a key entry point into the brain circuits that control sexual receptivity.

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    07/29/14 | Automated image-based tracking and its application in ecology.
    Dell AI, Bender JA, Branson K, Couzin ID, de Polavieja GG, Noldus LP, Pérez-Escudero A, Perona P, Straw AD, Wikelski M, Brose U
    Trends in Ecology and Evolution. 2014 Jul;29(7):417-428. doi: 10.1016/j.tree.2014.05.004

    The behavior of individuals determines the strength and outcome of ecological interactions, which drive population, community, and ecosystem organization. Bio-logging, such as telemetry and animal-borne imaging, provides essential individual viewpoints, tracks, and life histories, but requires capture of individuals and is often impractical to scale. Recent developments in automated image-based tracking offers opportunities to remotely quantify and understand individual behavior at scales and resolutions not previously possible, providing an essential supplement to other tracking methodologies in ecology. Automated image-based tracking should continue to advance the field of ecology by enabling better understanding of the linkages between individual and higher-level ecological processes, via high-throughput quantitative analysis of complex ecological patterns and processes across scales, including analysis of environmental drivers.

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    Baker Lab
    07/02/14 | Central brain neurons expressing doublesex regulate female receptivity in Drosophila.
    Zhou C, Pan Y, Robinett CC, Meissner GW, Baker BS
    Neuron. 2014 Jul 2;83(1):149-63. doi: 10.1016/j.neuron.2014.05.038

    Drosophila melanogaster females respond to male courtship by either rejecting the male or allowing copulation. The neural mechanisms underlying these female behaviors likely involve the integration of sensory information in the brain. Because doublesex (dsx) controls other aspects of female differentiation, we asked whether dsx-expressing neurons mediate virgin female receptivity to courting males. Using intersectional techniques to manipulate the activities of defined subsets of dsx-expressing neurons, we found that activation of neurons in either the pCd or pC1 clusters promotes receptivity, while silencing these neurons makes females unreceptive. Furthermore, pCd and pC1 neurons physiologically respond to the male-specific pheromone cis-vaccenyl acetate (cVA), while pC1 neurons also respond to male courtship song. The pCd and pC1 neurons expressing dsx in females do not express transcripts from the fruitless (fru) P1 promoter. Thus, virgin female receptivity is controlled at least in part by neurons that are distinct from those governing male courtship.

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    Sternson Lab
    07/08/14 | Chemogenetic tools to interrogate brain functions.
    Sternson SM, Roth BL
    Annual Review of Neuroscience. 2014 Jul 8;37:387-407. doi: 10.1146/annurev-neuro-071013-014048

    Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been developed for remotely controlling neuron function using small molecules that activate engineered receptors that can be targeted to cell types using genetic methods. Here we describe recent progress for approaches using genetically engineered receptors that selectively interact with small molecules. Called "chemogenetics," receptors with diverse cellular functions have been developed that facilitate the selective pharmacological control over a diverse range of cell-signaling processes, including electrical activity, for molecularly defined cell types. These tools have revealed remarkably specific behavioral physiological influences for molecularly defined cell types that are often intermingled with populations having different or even opposite functions.

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    07/20/14 | Fast, accurate reconstruction of cell lineages from large-scale fluorescence microscopy data.
    Amat F, Lemon W, Mossing DP, McDole K, Wan Y, Branson K, Myers EW, Keller PJ
    Nature Methods. 2014 Jul 20;11(9):951-8. doi: 10.1038/nmeth.3036

    The comprehensive reconstruction of cell lineages in complex multicellular organisms is a central goal of developmental biology. We present an open-source computational framework for the segmentation and tracking of cell nuclei with high accuracy and speed. We demonstrate its (i) generality by reconstructing cell lineages in four-dimensional, terabyte-sized image data sets of fruit fly, zebrafish and mouse embryos acquired with three types of fluorescence microscopes, (ii) scalability by analyzing advanced stages of development with up to 20,000 cells per time point at 26,000 cells min(-1) on a single computer workstation and (iii) ease of use by adjusting only two parameters across all data sets and providing visualization and editing tools for efficient data curation. Our approach achieves on average 97.0% linkage accuracy across all species and imaging modalities. Using our system, we performed the first cell lineage reconstruction of early Drosophila melanogaster nervous system development, revealing neuroblast dynamics throughout an entire embryo.

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