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9 Janelia Publications

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    12/20/17 | Advances in neural engineering for rehabilitation.
    Hu X, Zhao T, Yao J, Kuang Y, Yang Y
    Behavioural Neurology. 2017;2017:9240921. doi: 10.1155/2017/9240921
    11/03/17 | Topological and modality-specific representation of somatosensory information in the fly brain.
    Tsubouchi A, Yano T, Yokoyama TK, Murtin C, Otsuna H, Ito K
    Science (New York, N.Y.). 2017 11 03;358(6363):615-623. doi: 10.1126/science.aan4428

    Insects and mammals share similarities of neural organization underlying the perception of odors, taste, vision, sound, and gravity. We observed that insect somatosensation also corresponds to that of mammals. In Drosophila, the projections of all the somatosensory neuron types to the insect's equivalent of the spinal cord segregated into modality-specific layers comparable to those in mammals. Some sensory neurons innervate the ventral brain directly to form modality-specific and topological somatosensory maps. Ascending interneurons with dendrites in matching layers of the nerve cord send axons that converge to respective brain regions. Pathways arising from leg somatosensory neurons encode distinct qualities of leg movement information and play different roles in ground detection. Establishment of the ground pattern and genetic tools for neuronal manipulation should provide the basis for elucidating the mechanisms underlying somatosensation.

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    08/29/17 | Experimental and statistical reevaluation provides no evidence for Drosophila courtship song rhythms.
    Stern DL, Clemens J, Coen P, Calhoun AJ, Hogenesch JB, Arthur BJ, Murthy M
    Proceedings of the National Academy of Sciences of the United States of America. 2017 Aug 29;114(37):9978-83. doi: 10.1073/pnas.1707471114

    From 1980 to 1992, a series of influential papers reported on the discovery, genetics, and evolution of a periodic cycling of the interval between Drosophila male courtship song pulses. The molecular mechanisms underlying this periodicity were never described. To reinitiate investigation of this phenomenon, we previously performed automated segmentation of songs but failed to detect the proposed rhythm [Arthur BJ, et al. (2013) BMC Biol 11:11; Stern DL (2014) BMC Biol 12:38]. Kyriacou et al. [Kyriacou CP, et al. (2017) Proc Natl Acad Sci USA 114:1970-1975] report that we failed to detect song rhythms because (i) our flies did not sing enough and (ii) our segmenter did not identify many of the song pulses. Kyriacou et al. manually annotated a subset of our recordings and reported that two strains displayed rhythms with genotype-specific periodicity, in agreement with their original reports. We cannot replicate this finding and show that the manually annotated data, the original automatically segmented data, and a new dataset provide no evidence for either the existence of song rhythms or song periodicity differences between genotypes. Furthermore, we have reexamined our methods and analysis and find that our automated segmentation method was not biased to prevent detection of putative song periodicity. We conclude that there is no evidence for the existence of Drosophila courtship song rhythms.

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    07/25/17 | Experience-dependent shaping of hippocampal CA1 intracellular activity in novel and familiar environments.
    Cohen JD, Bolstad M, Lee AK
    eLife. 2017 Jul 25;6:. doi: 10.7554/eLife.23040

    The hippocampus is critical for producing stable representations of familiar spaces. How these representations arise is poorly understood, largely because changes to hippocampal inputs have not been measured during spatial learning. Here, using intracellular recording, we monitored inputs and plasticity-inducing complex spikes (CSs) in CA1 neurons while mice explored novel and familiar virtual environments. Inputs driving place field spiking increased in amplitude - often suddenly - during novel environment exploration. However, these increases were not sustained in familiar environments. Rather, the spatial tuning of inputs became increasingly similar across repeated traversals of the environment with experience - both within fields and throughout the whole environment. In novel environments, CSs were not necessary for place field formation. Our findings support a model in which initial inhomogeneities in inputs are amplified to produce robust place field activity, then plasticity refines this representation into one with less strongly modulated, but more stable, inputs for long-term storage.

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    07/18/17 | A connectome of a learning and memory center in the adult Drosophila brain.
    Takemura S, Aso Y, Hige T, Wong AM, Lu Z, Xu CS, Rivlin PK, Hess HF, Zhao T, Parag T, Berg S, Huang G, Katz WT, Olbris DJ, Plaza SM, Umayam LA, Aniceto R, Chang L, Lauchie S, et al
    eLife. 2017 Jul 18;6:e26975. doi: 10.7554/eLife.26975

    Understanding memory formation, storage and retrieval requires knowledge of the underlying neuronal circuits. In Drosophila, the mushroom body (MB) is the major site of associative learning. We reconstructed the morphologies and synaptic connections of all 983 neurons within the three functional units, or compartments, that compose the adult MB’s α lobe, using a dataset of isotropic 8-nm voxels collected by focused ion-beam milling scanning electron microscopy. We found that Kenyon cells (KCs), whose sparse activity encodes sensory information, each make multiple en passant synapses to MB output neurons (MBONs) in each compartment. Some MBONs have inputs from all KCs, while others differentially sample sensory modalities. Only six percent of KC>MBON synapses receive a direct synapse from a dopaminergic neuron (DAN). We identified two unanticipated classes of synapses, KC>DAN and DAN>MBON. DAN activation produces a slow depolarization of the MBON in these DAN>MBON synapses and can weaken memory recall.

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    07/13/17 | Mapping the neural substrates of behavior.
    Robie AA, Hirokawa J, Edwards AW, Umayam LA, Lee A, Phillips ML, Card GM, Korff W, Rubin GM, Simpson JH, Reiser MB, Branson KM
    Cell. 2017-07-13;170(2):393-406. doi: 10.1016/j.cell.2017.06.032

    Assigning behavioral functions to neural structures has long been a central goal in neuroscience and is a necessary first step toward a circuit-level understanding of how the brain generates behavior. Here, we map the neural substrates of locomotion and social behaviors for Drosophila melanogaster using automated machine-vision and machine-learning techniques. From videos of 400,000 flies, we quantified the behavioral effects of activating 2,204 genetically targeted populations of neurons. We combined a novel quantification of anatomy with our behavioral analysis to create brain-behavior correlation maps, which are shared as browsable web pages and interactive software. Based on these maps, we generated hypotheses of regions of the brain causally related to sensory processing, locomotor control, courtship, aggression, and sleep. Our maps directly specify genetic tools to target these regions, which we used to identify a small population of neurons with a role in the control of walking.

    •We developed machine-vision methods to broadly and precisely quantify fly behavior•We measured effects of activating 2,204 genetically targeted neuronal populations•We created whole-brain maps of neural substrates of locomotor and social behaviors•We created resources for exploring our results and enabling further investigation

    Machine-vision analyses of large behavior and neuroanatomy data reveal whole-brain maps of regions associated with numerous complex behaviors.

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    04/10/17 | Stem cell-intrinsic, seven-up-triggered temporal factor gradients diversify intermediate neural progenitors.
    Ren Q, Yang C, Liu Z, Sugino K, Mok K, He Y, Ito M, Nern A, Otsuna H, Lee T
    Current Biology : CB. 2017 Apr 10;27(9):1303-13. doi: 10.1016/j.cub.2017.03.047

    Building a sizable, complex brain requires both cellular expansion and diversification. One mechanism to achieve these goals is production of multiple transiently amplifying intermediate neural progenitors (INPs) from a single neural stem cell. Like mammalian neural stem cells, Drosophila type II neuroblasts utilize INPs to produce neurons and glia. Within a given lineage, the consecutively born INPs produce morphologically distinct progeny, presumably due to differential inheritance of temporal factors. To uncover the underlying temporal fating mechanisms, we profiled type II neuroblasts' transcriptome across time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding proteins (descending and ascending, respectively). Maintaining high Imp throughout serial INP production expands the number of neurons and glia with early temporal fate at the expense of cells with late fate. Conversely, precocious upregulation of Syp reduces the number of cells with early fate. Furthermore, we reveal that the transcription factor Seven-up initiates progression of the Imp/Syp gradients. Interestingly, neuroblasts that maintain initial Imp/Syp levels can still yield progeny with a small range of early fates. We therefore propose that the Seven-up-initiated Imp/Syp gradients create coarse temporal windows within type II neuroblasts to pattern INPs, which subsequently undergo fine-tuned subtemporal patterning.

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    01/31/17 | Multicut brings automated neurite segmentation closer to human performance.
    Beier T, Pape C, Rahaman N, Prange T, Berg S, Bock DD, Cardona A, Knott GW, Plaza SM, Scheffer LK, Koethe U, Kreshuk A, Hamprecht FA
    Nature Methods. 2017 Jan 31;14(2):101-102. doi: 10.1038/nmeth.4151
    01/01/17 | A statistical test for conserved RNA structure shows lack of evidence for structure in lncRNAs.
    Rivas E, Clements J, Eddy SR
    Nature Methods. 2017 Jan 31;14(1):45-8

    Many functional RNAs have an evolutionarily conserved secondary structure. Conservation of RNA base pairing induces pairwise covariations in sequence alignments. We developed a computational method, R-scape (RNA Structural Covariation Above Phylogenetic Expectation), that quantitatively tests whether covariation analysis supports the presence of a conserved RNA secondary structure. R-scape analysis finds no statistically significant support for proposed secondary structures of the long noncoding RNAs HOTAIR, SRA, and Xist.

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