Janelia Farm Research Campus

VA, United States

Janelia Farm Research Campus

VA, United States
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Mao T.,Janelia Farm Research Campus | Kusefoglu D.,Janelia Farm Research Campus | Kusefoglu D.,Oregon Health And Science University | Hooks B.,Janelia Farm Research Campus | And 3 more authors.
Neuron | Year: 2011

In the rodent vibrissal system, active sensation and sensorimotor integration are mediated in part by connections between barrel cortex and vibrissal motor cortex. Little is known about how these structures interact at the level of neurons. We used Channelrhodopsin-2 (ChR2) expression, combined with anterograde and retrograde labeling, to map connections between barrel cortex and pyramidal neurons in mouse motor cortex. Barrel cortex axons preferentially targeted upper layer (L2/3, L5A) neurons in motor cortex; input to neurons projecting back to barrel cortex was particularly strong. Barrel cortex input to deeper layers (L5B, L6) of motor cortex, including neurons projecting to the brainstem, was weak, despite pronounced geometric overlap of dendrites with axons from barrel cortex. Neurons in different layers received barrel cortex input within stereotyped dendritic domains. The cortico-cortical neurons in superficial layers of motor cortex thus couple motor and sensory signals and might mediate sensorimotor integration and motor learning. © 2011 Elsevier Inc.

Stachniak T.J.,Janelia Farm Research Campus | Stachniak T.J.,University of California at San Diego | Ghosh A.,University of California at San Diego | Ghosh A.,Hoffmann-La Roche | Sternson S.M.,Janelia Farm Research Campus
Neuron | Year: 2014

Brain function is mediated by neural circuit connectivity, and elucidating the role of connections is aided by techniques to block their output. We developed cell-type-selective, reversible synaptic inhibition tools for mammalian neural circuits by leveraging G protein signaling pathways to suppress synaptic vesicle release. Here, we find that the pharmacologically selective designer Gi-protein-coupled receptor hM4D is a presynaptic silencer in the presence of its cognate ligand clozapine-N-oxide (CNO). Activation of hM4D signaling sharply reduced synaptic release probability and synaptic current amplitude. To demonstrate the utility of this tool for neural circuit perturbations, we developed an axon-selective hM4D-neurexin variant and used spatially targeted intracranial CNO injections to localize circuit connections from the hypothalamus to the midbrain responsible for feeding behavior. This synaptic silencing approach is broadly applicable for cell-type-specific and axon projection-selective functional analysis of diverse neural circuits. © 2014 Elsevier Inc.

Guo Z.,Janelia Farm Research Campus | Li N.,Janelia Farm Research Campus | Huber D.,Janelia Farm Research Campus | Ophir E.,Janelia Farm Research Campus | And 4 more authors.
Neuron | Year: 2014

Perceptual decisions involve distributed cortical activity. Does information flow sequentially from one cortical area to another, or do networks of interconnected areas contribute at the same time? Herewe delineate when and how activity in specific areas drives a whisker-based decision in mice. Ashort-term memory component temporally separated tactile "sensation" and "action" (licking). Using optogenetic inhibition (spatial resolution, 2mm; temporal resolution, 100ms), we surveyed the neocortex for regions driving behavior during specific behavioral epochs. Barrel cortex was critical for sensation. During the short-term memory, unilateral inhibition of anterior lateral motor cortex biased responses to the ipsilateral side. Consistently, barrel cortex showed stimulus-specific activity during sensation, whereas motor cortex showed choice-specific preparatory activity and movement-related activity, consistent with roles in motor planning and movement. These results suggest serial information flow from sensory to motor areas during perceptual decision making. © 2014 Elsevier Inc.

News Article | December 16, 2015
Site: www.scientificcomputing.com

This 100X photograph shows the intake of a humped bladderwort (Utricularia gibba), a freshwater carnivorous plant, which traps insects and other small invertebrates. It was the 3rd place winner in the 2015 Nikon Small World Photomicrophotography Competition, which recognizes excellence in photography with the optical microscope. The photo was taken by Dr. Igor Siwanowicz of Hughes Medical Institute (HHMI), Janelia Farm Research Campus, Leonardo Lab in Ashburn, VA, using confocal microscopy.

Finn R.D.,Janelia Farm Research Campus | Gardner P.P.,University of Canterbury | Bateman A.,Wellcome Trust Sanger Institute
Nucleic Acids Research | Year: 2012

Wikipedia, the online encyclopedia, is the most famous wiki in use today. It contains over 3.7 million pages of content; with many pages written on scientific subject matters that include peer-reviewed citations, yet are written in an accessible manner and generally reflect the consensus opinion of the community. In this, the 19th Annual Database Issue of Nucleic Acids Research, there are 11 articles that describe the use of a wiki in relation to a biological database. In this commentary, we discuss how biological databases can be integrated with Wikipedia, thereby utilising the pre-existing infrastructure, tools and above all, large community of authors (or Wikipedians). The limitations to the content that can be included in Wikipedia are highlighted, with examples drawn from articles found in this issue and other wiki-based resources, indicating why other wiki solutions are necessary. We discuss the merits of using open wikis, like Wikipedia, versus other models, with particular reference to potential vandalism. Finally, we raise the question about the future role of dedicated database biocurators in context of the thousands of crowdsourced, community annotations that are now being stored in wikis. © The Author(s) 2011.

Khairy K.,Janelia Farm Research Campus | Howard J.,Max Planck Institute of Molecular Cell Biology and Genetics
Soft Matter | Year: 2011

An important open question in biophysics is to understand how mechanical forces shape membrane-bounded cells and their organelles. A general solution to this problem is to calculate the bending energy of an arbitrarily shaped membrane surface, which can include both lipids and cytoskeletal proteins, and minimize the energy subject to all mechanical constraints. However, the calculations are difficult to perform, especially for shapes that do not possess axial symmetry. We show that the spherical harmonics parameterization (SHP) provides an analytic description of shape that can be used to quickly and reliably calculate minimum energy shapes of both symmetric and asymmetric surfaces. Using this method, we probe the entire set of shapes predicted by the bilayer couple model, unifying work based on different computational approaches, and providing additional details of the transitions between different shape classes. In addition, we present new minimum-energy morphologies based on non-linear models of membrane skeletal elasticity that closely mimic extreme shapes of red blood cells. The SHP thus provides a versatile shape description that can be used to investigate forces that shape cells. © 2011 The Royal Society of Chemistry.

Vogelstein J.T.,Johns Hopkins University | Vogelstein J.T.,Duke University | Park Y.,Johns Hopkins University | Ohyama T.,Janelia Farm Research Campus | And 4 more authors.
Science | Year: 2014

A single nervous system can generatemany distinctmotor patterns. Identifying which neurons and circuits control which behaviors has been a laborious piecemeal process, usually for one observer-defined behavior at a time. We present a fundamentally different approach to neuron-behavior mapping. We optogenetically activated 1054 identified neuron lines in Drosophila larvae and tracked the behavioral responses from 37,780 animals. Application of multiscale unsupervised structure learning methods to the behavioral data enabled us to identify 29 discrete, statistically distinguishable, observer-unbiased behavioral phenotypes. Mapping the neural lines to the behavior(s) they evoke provides a behavioral reference atlas for neuron subsets covering a large fraction of larval neurons. This atlas is a starting point for connectivity- and activity-mapping studies to further investigate the mechanisms by which neurons mediate diverse behaviors.

Betley J.N.,Janelia Farm Research Campus | Cao Z.F.H.,Janelia Farm Research Campus | Ritola K.D.,Janelia Farm Research Campus | Sternson S.M.,Janelia Farm Research Campus
Cell | Year: 2013

Neural circuits for essential natural behaviors are shaped by selective pressure to coordinate reliable execution of flexible goal-directed actions. However, the structural and functional organization of survival-oriented circuits is poorly understood due to exceptionally complex neuroanatomy. This is exemplified by AGRP neurons, which are a molecularly defined population that is sufficient to rapidly coordinate voracious food seeking and consumption behaviors. Here, we use cell-type-specific techniques for neural circuit manipulation and projection-specific anatomical analysis to examine the organization of this critical homeostatic circuit that regulates feeding. We show that AGRP neuronal circuits use a segregated, parallel, and redundant output configuration. AGRP neuron axon projections that target different brain regions originate from distinct subpopulations, several of which are sufficient to independently evoke feeding. The concerted anatomical and functional analysis of AGRP neuron projection populations reveals a constellation of core forebrain nodes, which are part of an extended circuit that mediates feeding behavior. © 2013 Elsevier Inc.

Nawrocki E.P.,Janelia Farm Research Campus | Eddy S.R.,Janelia Farm Research Campus
RNA Biology | Year: 2013

A key step toward understanding a metagenomics data set is the identification of functional sequence elements within it, such as protein coding genes and structural RNAs. Relative to protein coding genes, structural RNAs are more difficult to identify because of their reduced alphabet size, lack of open reading frames and short length. Infernal is a software package that implements "covariance models" (CMs) for RNA homology search, which harness both sequence and structural conservation when searching for RNA homologs. Thanks to the added statistical signal inherent in the secondary structure conservation of many RNA families, Infernal is more powerful than sequence-only based methods such as BLAST and profile HMMs. Together with the Rfam database of CMs, Infernal is a useful tool for identifying RNAs in metagenomics data sets. © 2013 Landes Bioscience.

Sternson S.M.,Janelia Farm Research Campus | Nicholas Betley J.,Janelia Farm Research Campus | Cao Z.F.H.,Janelia Farm Research Campus
Current Opinion in Neurobiology | Year: 2013

How does an organism's internal state direct its actions? At one moment an animal forages for food with acrobatic feats such as tree climbing and jumping between branches. At another time, it travels along the ground to find water or a mate, exposing itself to predators along the way. These behaviors are costly in terms of energy or physical risk, and the likelihood of performing one set of actions relative to another is strongly modulated by internal state. For example, an animal in energy deficit searches for food and a dehydrated animal looks for water. The crosstalk between physiological state and motivational processes influences behavioral intensity and intent, but the underlying neural circuits are poorly understood. Molecular genetics along with optogenetic and pharmacogenetic tools for perturbing neuron function have enabled cell type-selective dissection of circuits that mediate behavioral responses to physiological state changes. Here, we review recent progress into neural circuit analysis of hunger in the mouse by focusing on a starvation-sensitive neuron population in the hypothalamus that is sufficient to promote voracious eating. We also consider research into the motivational processes that are thought to underlie hunger in order to outline considerations for bridging the gap between homeostatic and motivational neural circuits. © 2013 Elsevier Ltd.

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