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250 Publications

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    Zuker LabMouseLight
    01/15/15 | The neural representation of taste quality at the periphery.
    Barretto RP, Gillis-Smith S, Chandrashekar J, Yarmolinsky DA, Schnitzer MJ, Ryba NJ, Zuker CS
    Nature. 2015 Jan 15;517(7534):373-6. doi: 10.1038/nature13873

    The mammalian taste system is responsible for sensing and responding to the five basic taste qualities: sweet, sour, bitter, salty and umami. Previously, we showed that each taste is detected by dedicated taste receptor cells (TRCs) on the tongue and palate epithelium. To understand how TRCs transmit information to higher neural centres, we examined the tuning properties of large ensembles of neurons in the first neural station of the gustatory system. Here, we generated and characterized a collection of transgenic mice expressing a genetically encoded calcium indicator in central and peripheral neurons, and used a gradient refractive index microendoscope combined with high-resolution two-photon microscopy to image taste responses from ganglion neurons buried deep at the base of the brain. Our results reveal fine selectivity in the taste preference of ganglion neurons; demonstrate a strong match between TRCs in the tongue and the principal neural afferents relaying taste information to the brain; and expose the highly specific transfer of taste information between taste cells and the central nervous system.

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    01/13/15 | Distinct dopamine neurons mediate reward signals for short- and long-term memories.
    Yamagata N, Ichinose T, Aso Y, Placais P, Friedrich AB, Sima RJ, Preat T, Rubin GM, Tanimoto H
    Proceedings of the National Academy of Sciences of the United States of America. 2015 Jan 13;112(2):578-83. doi: 10.1073/pnas.1421930112

    Drosophila melanogaster can acquire a stable appetitive olfactory memory when the presentation of a sugar reward and an odor are paired. However, the neuronal mechanisms by which a single training induces long-term memory are poorly understood. Here we show that two distinct subsets of dopamine neurons in the fly brain signal reward for short-term (STM) and long-term memories (LTM). One subset induces memory that decays within several hours, whereas the other induces memory that gradually develops after training. They convey reward signals to spatially segregated synaptic domains of the mushroom body (MB), a potential site for convergence. Furthermore, we identified a single type of dopamine neuron that conveys the reward signal to restricted subdomains of the mushroom body lobes and induces long-term memory. Constant appetitive memory retention after a single training session thus comprises two memory components triggered by distinct dopamine neurons.

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    01/13/15 | Mapping social behavior-induced brain activation at cellular resolution in the mouse.
    Kim Y, Venkataraju KU, Pradhan K, Mende C, Taranda J, Turaga SC, Arganda-Carreras I, Ng L, Hawrylycz MJ, Rockland KS, Seung HS, Osten P
    Cell Reports. 2015 Jan 13;10(2):292-305. doi: 10.1016/j.celrep.2014.12.014

    Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here, we apply an automated method for mapping brain activation in the mouse in order to probe how sex-specific social behaviors are represented in the male brain. Our method uses the immediate-early-gene c-fos, a marker of neuronal activation, visualized by serial two-photon tomography: the c-fos-GFP+ neurons are computationally detected, their distribution is registered to a reference brain and a brain atlas, and their numbers are analyzed by statistical tests. Our results reveal distinct and shared female and male interaction-evoked patterns of male brain activation representing sex discrimination and social recognition. We also identify brain regions whose degree of activity correlates to specific features of social behaviors and estimate the total numbers and the densities of activated neurons per brain areas. Our study opens the door to automated screening of behavior-evoked brain activation in the mouse.

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    Cardona LabZlatic Lab
    01/13/15 | Sensory determinants of behavioral dynamics in Drosophila thermotaxis.
    Klein M, Afonso B, Vonner AJ, Hernandez-Nunez L, Berck M, Tabone CJ, Kane EA, Pieribone VA, Nitabach MN, Cardona A, Zlatic M, Sprecher SG, Gershow M, Garrity PA, Samuel AD
    Proceedings of the National Academy of Sciences of the United States of America. 2015 Jan 13;112(2):E220-9. doi: 10.1073/pnas.1416212112

    Complex animal behaviors are built from dynamical relationships between sensory inputs, neuronal activity, and motor outputs in patterns with strategic value. Connecting these patterns illuminates how nervous systems compute behavior. Here, we study Drosophila larva navigation up temperature gradients toward preferred temperatures (positive thermotaxis). By tracking the movements of animals responding to fixed spatial temperature gradients or random temperature fluctuations, we calculate the sensitivity and dynamics of the conversion of thermosensory inputs into motor responses. We discover three thermosensory neurons in each dorsal organ ganglion (DOG) that are required for positive thermotaxis. Random optogenetic stimulation of the DOG thermosensory neurons evokes behavioral patterns that mimic the response to temperature variations. In vivo calcium and voltage imaging reveals that the DOG thermosensory neurons exhibit activity patterns with sensitivity and dynamics matched to the behavioral response. Temporal processing of temperature variations carried out by the DOG thermosensory neurons emerges in distinct motor responses during thermotaxis.

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    01/08/15 | Artificial metalloenzymes derived from three-helix bundles.
    Tebo AG, Pecoraro VL
    Current Opinion in Chemical Biology. 01/2015;25C:65 – 70. doi: 10.1016/j.cbpa.2014.12.034

    Three-helix bundles and coiled-coil motifs are well-established de novo designed scaffolds that have been investigated for their metal-binding and catalytic properties. Satisfaction of the primary coordination sphere for a given metal is sufficient to introduce catalytic activity and a given structure may catalyze different reactions dependent on the identity of the incorporated metal. Here we describe recent contributions in the de novo design of metalloenzymes based on three-helix bundles and coiled-coil motifs, focusing on non-heme systems for hydrolytic and redox chemistry.

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    01/08/15 | Proper migration and axon outgrowth of zebrafish cranial motoneuron subpopulations require the cell adhesion molecule MDGA2A.
    Ingold E, Vom Berg-Maurer CM, Burckhardt CJ, Lehnherr A, Rieder P, Keller PJ, Stelzer EH, Greber UF, Neuhauss SC, Gesemann M
    Biology Open. 2015;4(2):146-54. doi: 10.1242/bio.20148482

    The formation of functional neuronal circuits relies on accurate migration and proper axonal outgrowth of neuronal precursors. On the route to their targets migrating cells and growing axons depend on both, directional information from neurotropic cues and adhesive interactions mediated via extracellular matrix molecules or neighbouring cells. The inactivation of guidance cues or the interference with cell adhesion can cause severe defects in neuronal migration and axon guidance. In this study we have analyzed the function of the MAM domain containing glycosylphosphatidylinositol anchor 2A (MDGA2A) protein in zebrafish cranial motoneuron development. MDGA2A is prominently expressed in distinct clusters of cranial motoneurons, especially in the ones of the trigeminal and facial nerves. Analyses of MDGA2A knockdown embryos by light sheet and confocal microscopy revealed impaired migration and aberrant axonal outgrowth of these neurons; suggesting that adhesive interactions mediated by MDGA2A are required for the proper arrangement and outgrowth of cranial motoneuron subtypes.

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    01/07/15 | Adenotrophic viviparity in tsetse flies: potential for population control and as an insect model for lactation.
    Benoit JB, Attardo GM, Baumann AA, Michalkova V, Aksoy S
    Annual Review of Entomology. 2015 Jan 7;60:351-71. doi: 10.1146/annurev-ento-010814-020834

    Tsetse flies (Glossina spp.), vectors of African trypanosomes, are distinguished by their specialized reproductive biology, defined by adenotrophic viviparity (maternal nourishment of progeny by glandular secretions followed by live birth). This trait has evolved infrequently among insects and requires unique reproductive mechanisms. A key event in Glossina reproduction involves the transition between periods of lactation and nonlactation (dry periods). Increased lipolysis, nutrient transfer to the milk gland, and milk-specific protein production characterize lactation, which terminates at the birth of the progeny and is followed by a period of involution. The dry stage coincides with embryogenesis of the progeny, during which lipid reserves accumulate in preparation for the next round of lactation. The obligate bacterial symbiont Wigglesworthia glossinidia is critical to tsetse reproduction and likely provides B vitamins required for metabolic processes underlying lactation and/or progeny development. Here we describe findings that utilized transcriptomics, physiological assays, and RNA interference-based functional analysis to understand different components of adenotrophic viviparity in tsetse flies.

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    01/01/15 | NAD⁺/NADH metabolism and NAD⁺-dependent enzymes in cell death and ischemic brain injury: current advances and therapeutic implications.
    Ma Y, Nie H, Chen H, Li J, Hong Y, Wang B, Wang C, Zhang J, Cao W, Zhang M, Xu Y, Ding X, Yin SK, Qu X, Ying W
    Curr Med Chem. 2015;22(10):1239-47. doi: 10.2174/0929867322666150209154420

    NAD(+) and NADH play crucial roles in a variety of biological processes including energy metabolism, mitochondrial functions, and gene expression. Multiple studies have indicated that NAD(+) administration can profoundly decrease oxidative cell death as well as ischemic and traumatic brain injury, suggesting NAD(+) metabolism as a promising therapeutic target for cerebral ischemia and head injury. Cumulating evidence has suggested that NAD(+) can produce its protective effects by multiple mechanisms, including preventing mitochondrial alterations, enhancing energy metabolism, preventing virtually all forms of cell death including apoptosis, necrosis and autophagy, inhibiting inflammation, directly increasing antioxidation capacity of cells and tissues, and activating SIRT1. Increasing evidence has also suggested that NADH metabolism is a potential therapeutic target for treating several neurological disorders. A number of studies have further indicated that multiple NAD(+)-dependent enzymes such as sirtuins, polymerase(ADP-ribose) polymerases (PARPs) and CD38 mediate cell death and multiple biological processes. In this article, an overview of the recent findings regarding the roles of NAD(+)/NADH and NAD(+)-dependent enzymes in cell death and ischemic brain injury is provided. These findings have collectively indicated that NAD(+)/NADH and NAD(+)-dependent enzymes play fundamental roles in oxidative stress-induced cell death and ischemic brain injury, which may become promising therapeutic targets for brain ischemia and multiple other neurological disorders.

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    01/01/15 | Photocontrollable fluorescent proteins for superresolution imaging.
    Shcherbakova DM, Sengupta P, Lippincott-Schwartz J, Verkhusha VV
    Annual review of biophysics. 2014;43:303-29. doi: 10.1146/annurev-biophys-051013-022836

    Superresolution fluorescence microscopy permits the study of biological processes at scales small enough to visualize fine subcellular structures that are unresolvable by traditional diffraction-limited light microscopy. Many superresolution techniques, including those applicable to live cell imaging, utilize genetically encoded photocontrollable fluorescent proteins. The fluorescence of these proteins can be controlled by light of specific wavelengths. In this review, we discuss the biochemical and photophysical properties of photocontrollable fluorescent proteins that are relevant to their use in superresolution microscopy. We then describe the recently developed photoactivatable, photoswitchable, and reversibly photoswitchable fluorescent proteins, and we detail their particular usefulness in single-molecule localization-based and nonlinear ensemble-based superresolution techniques. Finally, we discuss recent applications of photocontrollable proteins in superresolution imaging, as well as how these applications help to clarify properties of intracellular structures and processes that are relevant to cell and developmental biology, neuroscience, cancer biology and biomedicine.

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    01/01/15 | Short-term plasticity based network model of place cells dynamics.
    Romani S, Tsodyks M
    Hippocampus. 2015 Jan;25(1):94-105. doi: 10.1002/hipo.22355

    Rodent hippocampus exhibits strikingly different regimes of population activity in different behavioral states. During locomotion, hippocampal activity oscillates at theta frequency (5-12 Hz) and cells fire at specific locations in the environment, the place fields. As the animal runs through a place field, spikes are emitted at progressively earlier phases of the theta cycles. During immobility, hippocampus exhibits sharp irregular bursts of activity, with occasional rapid orderly activation of place cells expressing a possible trajectory of the animal. The mechanisms underlying this rich repertoire of dynamics are still unclear. We developed a novel recurrent network model that accounts for the observed phenomena. We assume that the network stores a map of the environment in its recurrent connections, which are endowed with short-term synaptic depression. We show that the network dynamics exhibits two different regimes that are similar to the experimentally observed population activity states in the hippocampus. The operating regime can be solely controlled by external inputs. Our results suggest that short-term synaptic plasticity is a potential mechanism contributing to shape the population activity in hippocampus.

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