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2432 Janelia Publications

Showing 1421-1430 of 2432 results
Lee (Albert) LabSternson Lab
06/16/16 | Near-perfect synaptic integration by Nav1.7 in hypothalamic neurons regulates body weight.
Branco T, Tozer A, Magnus CJ, Sugino K, Tanaka S, Lee AK, Wood JN, Sternson SM
Cell. 2016 Jun 16;165(7):1749-61. doi: 10.1016/j.cell.2016.05.019

Neurons are well suited for computations on millisecond timescales, but some neuronal circuits set behavioral states over long time periods, such as those involved in energy homeostasis. We found that multiple types of hypothalamic neurons, including those that oppositely regulate body weight, are specialized as near-perfect synaptic integrators that summate inputs over extended timescales. Excitatory postsynaptic potentials (EPSPs) are greatly prolonged, outlasting the neuronal membrane time-constant up to 10-fold. This is due to the voltage-gated sodium channel Nav1.7 (Scn9a), previously associated with pain-sensation but not synaptic integration. Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EPSP duration, synaptic integration, and altered body weight in mice. In vivo whole-cell recordings in the hypothalamus confirmed near-perfect synaptic integration. These experiments show that integration of synaptic inputs over time by Nav1.7 is critical for body weight regulation and reveal a mechanism for synaptic control of circuits regulating long term homeostatic functions.

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Gonen LabDruckmann Lab
06/15/16 | Design of a hyperstable 60-subunit protein icosahedron.
Hsia Y, Bale JB, Gonen S, Shi D, Sheffler W, Fong KK, Nattermann U, Xu C, Huang P, Ravichandran R, Yi S, Davis TN, Gonen T, King NP, Baker D
Nature. 2016 Jun 15:. doi: 10.1038/nature18010

The icosahedron is the largest of the Platonic solids, and icosahedral protein structures are widely used in biological systems for packaging and transport. There has been considerable interest in repurposing such structures for applications ranging from targeted delivery to multivalent immunogen presentation. The ability to design proteins that self-assemble into precisely specified, highly ordered icosahedral structures would open the door to a new generation of protein containers with properties custom-tailored to specific applications. Here we describe the computational design of a 25-nanometre icosahedral nanocage that self-assembles from trimeric protein building blocks. The designed protein was produced in Escherichia coli, and found by electron microscopy to assemble into a homogenous population of icosahedral particles nearly identical to the design model. The particles are stable in 6.7 molar guanidine hydrochloride at up to 80 degrees Celsius, and undergo extremely abrupt, but reversible, disassembly between 2 molar and 2.25 molar guanidinium thiocyanate. The icosahedron is robust to genetic fusions: one or two copies of green fluorescent protein (GFP) can be fused to each of the 60 subunits to create highly fluorescent 'standard candles' for use in light microscopy, and a designed protein pentamer can be placed in the centre of each of the 20 pentameric faces to modulate the size of the entrance/exit channels of the cage. Such robust and customizable nanocages should have considerable utility in targeted drug delivery, vaccine design and synthetic biology.

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06/15/16 | Efficient convolutional neural networks for pixelwise classification on heterogeneous hardware systems.
Tschopp F, Martel JN, Turaga SC, Cook M, Funke J
IEEE 13th International Symposium on Biomedical Imaging: From Nano to Macro. 2016 Jun 15:. doi: 10.1109/ISBI.2016.7493487

With recent advances in high-throughput Electron Microscopy (EM) imaging it is now possible to image an entire nervous system of organisms like Drosophila melanogaster. One of the bottlenecks to reconstruct a connectome from these large volumes (œ 100 TiB) is the pixel-wise prediction of membranes. The time it would typically take to process such a volume using a convolutional neural network (CNN) with a sliding window approach is in the order of years on a current GPU. With sliding windows, however, a lot of redundant computations are carried out. In this paper, we present an extension to the Caffe library to increase throughput by predicting many pixels at once. On a sliding window network successfully used for membrane classification, we show that our method achieves a speedup of up to 57×, maintaining identical prediction results.

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Saalfeld LabFly Functional Connectome
06/15/16 | Robust registration of calcium images by learned contrast synthesis.
Bogovic JA, Hanslovsky P, Wong AM, Saalfeld S
IEEE 13th International Symposium on Biomedical Imaging: From Nano to Macro. 2016 Jun 15:. doi: 10.1109/ISBI.2016.7493463

Multi-modal image registration is a challenging task that is vital to fuse complementary signals for subsequent analyses. Despite much research into cost functions addressing this challenge, there exist cases in which these are ineffective. In this work, we show that (1) this is true for the registration of in-vivo Drosophila brain volumes visualizing genetically encoded calcium indicators to an nc82 atlas and (2) that machine learning based contrast synthesis can yield improvements. More specifically, the number of subjects for which the registration outright failed was greatly reduced (from 40% to 15%) by using a synthesized image.

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06/14/16 | A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging.
Sofroniew NJ, Flickinger D, King J, Svoboda K
eLife. 2016 Jun 14;5:e14472. doi: 10.7554/eLife.14472

Imaging is used to map activity across populations of neurons. Microscopes with cellular resolution have small (<1 millimeter) fields of view and cannot simultaneously image activity distributed across multiple brain areas. Typical large field of view microscopes do not resolve single cells, especially in the axial dimension. We developed a 2-photon random access mesoscope (2p-RAM) that allows high-resolution imaging anywhere within a volume spanning multiple brain areas (∅ 5 mm x 1 mm cylinder). 2p-RAM resolution is near diffraction limited (lateral, 0.66 μm, axial 4.09 μm at the center; excitation wavelength = 970 nm; numerical aperture = 0.6) over a large range of excitation wavelengths. A fast three-dimensional scanning system allows efficient sampling of neural activity in arbitrary regions of interest across the entire imaging volume. We illustrate the use of the 2p-RAM by imaging neural activity in multiple, non-contiguous brain areas in transgenic mice expressing protein calcium sensors.

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06/14/16 | Neural circuits that drive startle behavior, with a focus on the Mauthner cells and spiral fiber neurons of fishes.
Hale ME, Katz HR, Peek MY, Fremont RT
Journal of Neurogenetics. 2016 Jun;30(2):89-100. doi: 10.1080/01677063.2016.1182526

Startle behaviors are rapid, high-performance motor responses to threatening stimuli. Startle responses have been identified in a broad range of species across animal diversity. For investigations of neural circuit structure and function, these behaviors offer a number of benefits, including that they are driven by large and identifiable neurons and their neural control is simple in comparison to other behaviors. Among vertebrates, the best-known startle circuit is the Mauthner cell circuit of fishes. In recent years, genetic approaches in zebrafish have provided key tools for morphological and physiological dissection of circuits and greatly extended understanding of their architecture. Here we discuss the startle circuit of fishes, with a focus on the Mauthner cells and associated interneurons called spiral fiber neurons and we add new observations on hindbrain circuit organization. We also briefly review and compare startle circuits of several other taxa, paying particular attention to how movement direction is controlled.

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06/10/16 | in vivo brain imaging with adaptive optical microscope.
Wang K, Sun W, Ji N, Betzig E
Conference on Lasers and Electro-Optics (CLEO): Applications and Technology. 2016 Jun :AM40.1. doi: 10.1364/CLEO_AT.2016.AM4O.1

The diffraction limited resolution of two photon and confocal microscope can be recovered using adaptive optics to explore the detailed neuronal network in the brains of zebrafish and mouse in vivo.

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Magee LabPodgorski Lab
06/08/16 | Brain heating induced by near infrared lasers during multi-photon microscopy.
Podgorski K, Ranganathan GN
Journal of Neurophysiology. 2016 Jun 8;116(3):1012-23. doi: 10.1152/jn.00275.2016

Two-photon imaging and optogenetic stimulation rely on high illumination powers, particularly for state-of-the-art applications that target deeper structures, achieve faster measurements, or probe larger brain areas. However, little information is available on heating and resulting damage induced by high-power illumination in the brain. Here we used thermocouple probes and quantum dot nanothermometers to measure temperature changes induced by two-photon microscopy in the neocortex of awake and anaesthetized mice. We characterized heating as a function of wavelength, exposure time, and distance from the center of illumination. Although total power is highest near the surface of the brain, heating was most severe hundreds of microns below the focal plane, due to heat dissipation through the cranial window. Continuous illumination of a 1mm2 area produced a peak temperature increase of approximately 1.8°C/100mW. Continuous illumination with powers above 250 mW induced lasting damage, detected with immunohistochemistry against Iba1, GFAP, heat shock proteins, and activated Caspase-3. Higher powers were usable in experiments with limited duty ratios, suggesting an approach to mitigate damage in high-power microscopy experiments.

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Grigorieff Lab
06/07/16 | Frealign: an exploratory tool for single-particle cryo-EM.
Grigorieff N
Methods in Enzymology. 2016 Jun 07:. doi: 10.1016/bs.mie.2016.04.013

Frealign is a software tool designed to process electron microscope images of single molecules and complexes to obtain reconstructions at the highest possible resolution. It provides a number of refinement parameters and options that allow users to tune their refinement to achieve specific goals, such as masking to classify selected regions within a particle, control over the refinement of specific alignment parameters to accommodate various data collection schemes, refinement of pseudosymmetric particles, and generation of initial maps. This chapter provides a general overview of Frealign functions and a more detailed guide to using Frealign in typical scenarios.

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06/06/16 | The insect central complex.
Turner-Evans DB, Jayaraman V
Current Biology : CB. 2016 Jun 06;26(11):R453-7. doi: 10.1016/j.cub.2016.04.006

Hordes of tourists flock to Washington, D.C. every spring to see the cherry trees blossom. Once in the city, they must find their way to the Tidal Basin where the Japanese trees grow. Fortunately, a number of visual landmarks can help them to navigate. In 1910, the United States Congress passed The Height of Buildings Act, limiting the elevation of commercial and residential structures in D.C. to 130 feet. Thus, the 555-foot-tall Washington Monument often looms large against the horizon, serving as an anchor point to help set the tourists' sense of direction. Once their heading is set, they can lose sight of the monument behind buildings or groups of tall Scandinavian visitors and still use their internal compass to navigate to the Basin. This compass keeps track of their paces and turns and updates their sense of where they are and where they need to go. Yet while their heading informs their actions, it does not dictate them. Tourists who have been to D.C. in the past can, for example, use remembered views to alter their routes to avoid crowds. On an even finer scale, their leg movements also depend on their current state - they might increase the frequency and length of their strides if hunger pangs compete with their desire to see cherry blossoms, for example. The way in which these disparate cues and motivations influence exploration is a neuroscience mystery across creatures large and small.

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