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1339 Janelia Publications

Showing 11-20 of 1339 results
04/02/18 | Colour vision: A fresh view of lateral inhibition in Drosophila.
Longden KD
Current Biology : CB. 2018 Apr 02;28(7):R308-R311. doi: 10.1016/j.cub.2018.02.052

A recent study reports a novel form of lateral inhibition between photoreceptors supporting colour vision in the vinegar fly, Drosophila melanogaster.

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04/01/18 | 50 Hz volumetric functional imaging with continuously adjustable depth of focus.
Lu R, Tanimoto M, Koyama M, Na J
Biomedical Optics Express. 2018 Apr;9(4):1964-76. doi: 10.1364/BOE.9.001964

Understanding how neural circuits control behavior requires monitoring a large population of neurons with high spatial resolution and volume rate. Here we report an axicon-based Bessel beam module with continuously adjustable depth of focus (CADoF), that turns frame rate into volume rate by extending the excitation focus in the axial direction while maintaining high lateral resolutions. Cost-effective and compact, this CADoF Bessel module can be easily integrated into existing two-photon fluorescence microscopes. Simply translating one of the relay lenses along its optical axis enabled continuous adjustment of the axial length of the Bessel focus. We used this module to simultaneously monitor activity of spinal projection neurons extending over 60 µm depth in larval zebrafish at 50 Hz volume rate with adjustable axial extent of the imaged volume.

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04/01/18 | Evaluating the potential of using quantum dots for monitoring electrical signals in neurons.
Efros AL, Delehanty JB, Huston AL, Medintz IL, Barbic M, Harris TD
Nature Nanotechnology. 2018 Apr;13(4):278-288. doi: 10.1038/s41565-018-0107-1

Success in the projects aimed at providing an advanced understanding of the brain is directly predicated on making critical advances in nanotechnology. This Perspective addresses the unique interface of neuroscience and nanomaterials by considering the foundational problem of sensing neuron membrane voltage and offers a potential solution that may be facilitated by a prototypical nanomaterial. Despite substantial improvements, the visualization of instantaneous voltage changes within individual neurons, whether in cell culture or in vivo, at both the single-cell and network level at high speed remains complex and problematic. The unique properties of semiconductor quantum dots (QDs) have made them powerful fluorophores for bioimaging. What is not widely appreciated, however, is that QD photoluminescence is exquisitely sensitive to proximal electric fields. This property should be suitable for sensing voltage changes that occur in the active neuronal membrane. Here, we examine the potential role of QDs in addressing the important challenge of real-time optical voltage imaging.

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04/01/18 | Functional Imaging and Optogenetics in .
Simpson JH, Looger LL
Genetics. 2018 Apr;208(4):1291-1309. doi: 10.1534/genetics.117.300228

Understanding how activity patterns in specific neural circuits coordinate an animal's behavior remains a key area of neuroscience research. Genetic tools and a brain of tractable complexity make a premier model organism for these studies. Here, we review the wealth of reagents available to map and manipulate neuronal activity with light.

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04/01/18 | Unnecessary tension.
Cox JD, Seltzer MJ
Lab Animal. 2018 Apr;47(4):91. doi: 10.1038/s41684-018-0024-9
03/29/18 | Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb.
Wolff C, Tinevez J, Pietzsch T, Stamataki E, Harich B, Guignard L, Preibisch S, Shorte S, Keller PJ, Tomancak P, Pavlopoulos A
eLife. 2018 Mar 29:. doi: 10.7554/eLife.34410

During development, coordinated cell behaviors orchestrate tissue and organ morphogenesis. Detailed descriptions of cell lineages and behaviors provide a powerful framework to elucidate the mechanisms of morphogenesis. To study the cellular basis of limb development, we imaged transgenic fluorescently-labeled embryos from the crustacean Parhyale hawaiensis with multi-view light-sheet microscopy at high spatiotemporal resolution over several days of embryogenesis. The cell lineage of outgrowing thoracic limbs was reconstructed at single-cell resolution with new software called Massive Multi-view Tracker (MaMuT). In silico clonal analyses suggested that the early limb primordium becomes subdivided into anterior-posterior and dorsal-ventral compartments whose boundaries intersect at the distal tip of the growing limb. Limb-bud formation is associated with spatial modulation of cell proliferation, while limb elongation is also driven by preferential orientation of cell divisions along the proximal-distal growth axis. Cellular reconstructions were predictive of the expression patterns of limb development genes including the BMP morphogen Decapentaplegic.

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03/28/18 | Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.
Shen K, Huang RK, Brignole EJ, Condon KJ, Valenstein ML, Chantranupong L, Bomaliyamu A, Choe A, Hong C, Yu Z, Sabatini DM
Nature. 2018 Mar 28:. doi: 10.1038/nature26158

Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.

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03/28/18 | Dedicated photoreceptor pathways in Drosophila larvae mediate navigation by processing either spatial or temporal cues.
Humberg T, Bruegger P, Afonso B, Zlatic M, Truman JW, Gershow M, Samuel A, Sprecher SG
Nature Communications. 2018 Mar 28;9(1):1260. doi: 10.1038/s41467-018-03520-5

To integrate changing environmental cues with high spatial and temporal resolution is critical for animals to orient themselves. Drosophila larvae show an effective motor program to navigate away from light sources. How the larval visual circuit processes light stimuli to control navigational decision remains unknown. The larval visual system is composed of two sensory input channels, Rhodopsin5 (Rh5) and Rhodopsin6 (Rh6) expressing photoreceptors (PRs). We here characterize how spatial and temporal information are used to control navigation. Rh6-PRs are required to perceive temporal changes of light intensity during head casts, while Rh5-PRs are required to control behaviors that allow navigation in response to spatial cues. We characterize how distinct behaviors are modulated and identify parallel acting and converging features of the visual circuit. Functional features of the larval visual circuit highlight the principle of how early in a sensory circuit distinct behaviors may be computed by partly overlapping sensory pathways.

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03/28/18 | Low-dimensional and monotonic preparatory activity in mouse anterior lateral motor cortex.
Inagaki HK, Inagaki M, Romani S, Svoboda K
The Journal of Neuroscience : the official journal of the Society for Neuroscience. 2018 Mar 28:. doi: 10.1523/JNEUROSCI.3152-17.2018

Neurons in multiple brain regions fire trains of action potentials anticipating specific movements, but this 'preparatory activity' has not been systematically compared across behavioral tasks. We compared preparatory activity in auditory and tactile delayed-response tasks in male mice. Skilled, directional licking was the motor output. The anterior lateral motor cortex (ALM) is necessary for motor planning in both tasks. Multiple features of ALM preparatory activity during the delay epoch were similar across tasks. First, majority of neurons showed direction-selective activity and spatially intermingled neurons were selective for either movement direction. Second, many cells showed mixed coding of sensory stimulus and licking direction, with a bias toward licking direction. Third, delay activity was monotonic and low-dimensional. Fourth, pairs of neurons with similar direction selectivity showed high spike-count correlations. Our study forms the foundation to analyze the neural circuit mechanisms underlying preparatory activity in a genetically tractable model organism.Short-term memories link events separated in time. Neurons in frontal cortex fire trains of action potentials anticipating specific movements, often seconds before the movement. This 'preparatory activity' has been observed in multiple brain regions, but has rarely been compared systematically across behavioral tasks in the same brain region. To identify common features of preparatory activity, we developed and compared preparatory activity in auditory and tactile delayed-response tasks in mice. The same cortical area is necessary for both tasks. Multiple features of preparatory activity, measured with high-density silicon probes, were similar across tasks. We find that preparatory activity is low-dimensional and monotonic. Our study forms the foundation to analyze the circuit mechanisms underlying preparatory activity in a genetically tractable model organism.

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03/27/18 | Dynamic cues for whisker-based object localization: An analytical solution to vibration during active whisker touch.
Vaxenburg R, Wyche I, Svoboda K, Efros AL, Hires SA
PLoS Computational Biology. 2018 Mar 27;14(3):e1006032. doi: 10.1371/journal.pcbi.1006032

Vibrations are important cues for tactile perception across species. Whisker-based sensation in mice is a powerful model system for investigating mechanisms of tactile perception. However, the role vibration plays in whisker-based sensation remains unsettled, in part due to difficulties in modeling the vibration of whiskers. Here, we develop an analytical approach to calculate the vibrations of whiskers striking objects. We use this approach to quantify vibration forces during active whisker touch at a range of locations along the whisker. The frequency and amplitude of vibrations evoked by contact are strongly dependent on the position of contact along the whisker. The magnitude of vibrational shear force and bending moment is comparable to quasi-static forces. The fundamental vibration frequencies are in a detectable range for mechanoreceptor properties and below the maximum spike rates of primary sensory afferents. These results suggest two dynamic cues exist that rodents can use for object localization: vibration frequency and comparison of vibrational to quasi-static force magnitude. These complement the use of quasi-static force angle as a distance cue, particularly for touches close to the follicle, where whiskers are stiff and force angles hardly change during touch. Our approach also provides a general solution to calculation of whisker vibrations in other sensing tasks.

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