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112 Janelia Publications

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    12/18/12 | Visual neuroscience: a moving story of neuromodulation.
    Jayaraman V
    Current Biology. 2012 Dec 18;22(24):R1057-9. doi: 10.1016/j.cub.2012.11.041

    The visual neurons of many animals process sensory input differently depending on the animal’s state of locomotion. Now, new work in Drosophila melanogaster shows that neuromodulatory neurons active during flight boost responses of neurons in the visual system.

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    Svoboda LabMagee Lab
    12/13/12 | Nonlinear dendritic integration of sensory and motor input during an active sensing task.
    Xu N, Harnett MT, Williams SR, Huber D, O’Connor DH, Svoboda K, Magee JC
    Nature. 2012 Dec 13;492:247-51. doi: 10.1038/nature11601

    Active dendrites provide neurons with powerful processing capabilities. However, little is known about the role of neuronal dendrites in behaviourally related circuit computations. Here we report that a novel global dendritic nonlinearity is involved in the integration of sensory and motor information within layer 5 pyramidal neurons during an active sensing behaviour. Layer 5 pyramidal neurons possess elaborate dendritic arborizations that receive functionally distinct inputs, each targeted to spatially separate regions. At the cellular level, coincident input from these segregated pathways initiates regenerative dendritic electrical events that produce bursts of action potential output and circuits featuring this powerful dendritic nonlinearity can implement computations based on input correlation. To examine this in vivo we recorded dendritic activity in layer 5 pyramidal neurons in the barrel cortex using two-photon calcium imaging in mice performing an object-localization task. Large-amplitude, global calcium signals were observed throughout the apical tuft dendrites when active touch occurred at particular object locations or whisker angles. Such global calcium signals are produced by dendritic plateau potentials that require both vibrissal sensory input and primary motor cortex activity. These data provide direct evidence of nonlinear dendritic processing of correlated sensory and motor information in the mammalian neocortex during active sensation.

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    12/07/12 | Noninvasive imaging beyond the diffraction limit of 3D dynamics in thickly fluorescent specimens.
    Gao L, Shao L, Higgins CD, Poulton JS, Peifer M, Davidson MW, Wu X, Goldstein B, Betzig E
    Cell. 2012 Dec 7;151(6):1370-85. doi: 10.1016/j.cell.2012.10.008

    Optical imaging of the dynamics of living specimens involves tradeoffs between spatial resolution, temporal resolution, and phototoxicity, made more difficult in three dimensions. Here, however, we report that rapid three-dimensional (3D) dynamics can be studied beyond the diffraction limit in thick or densely fluorescent living specimens over many time points by combining ultrathin planar illumination produced by scanned Bessel beams with super-resolution structured illumination microscopy. We demonstrate in vivo karyotyping of chromosomes during mitosis and identify different dynamics for the actin cytoskeleton at the dorsal and ventral surfaces of fibroblasts. Compared to spinning disk confocal microscopy, we demonstrate substantially reduced photodamage when imaging rapid morphological changes in D. discoideum cells, as well as improved contrast and resolution at depth within developing C. elegans embryos. Bessel beam structured plane illumination thus promises new insights into complex biological phenomena that require 4D subcellular spatiotemporal detail in either a single or multicellular context.

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    Riddiford Lab
    12/01/12 | How does juvenile hormone control insect metamorphosis and reproduction?
    Riddiford LM
    General and Comparative Endocrinology. 2012 Dec 1;179(3):477-84. doi: 10.1016/j.ygcen.2012.06.001

    In insects juvenile hormone (JH) regulates both metamorphosis and reproduction. This lecture focuses on our current understanding of JH action at the molecular level in both of these processes based primarily on studies in the tobacco hornworm Manduca sexta, the flour beetle Tribolium castaneum, the mosquito Aedes aegypti, and the fruit fly Drosophila melanogaster. The roles of the JH receptor complex and the transcription factors that it regulates during larval molting and metamorphosis are summarized. Also highlighted are the intriguing interactions of the JH and insulin signaling pathways in both imaginal disc development and vitellogenesis. Critical actions of JH and its receptor in the timing of maturation of the adult optic lobe and of female receptivity in Drosophila are also discussed.

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    12/01/12 | JAABA: interactive machine learning for automatic annotation of animal behavior.
    Kabra M, Robie AA, Rivera-Alba M, Branson S, Branson K
    Nature Methods. 2012 Dec;10:64-7

    We present a machine learning–based system for automatically computing interpretable, quantitative measures of animal behavior. Through our interactive system, users encode their intuition about behavior by annotating a small set of video frames. These manual labels are converted into classifiers that can automatically annotate behaviors in screen-scale data sets. Our general-purpose system can create a variety of accurate individual and social behavior classifiers for different organisms, including mice and adult and larval Drosophila.

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    12/01/12 | The effort to make mosaic analysis a household tool.
    Xu T, Rubin GM
    Development. 2012 Dec;139(24):4501-3. doi: 10.1242/dev.085183

    The analysis of genetic mosaics, in which an animal carries populations of cells with differing genotypes, is a powerful tool for understanding developmental and cell biology. In 1990, we set out to improve the methods used to make genetic mosaics in Drosophila by taking advantage of recently developed approaches for genome engineering. These efforts led to the work described in our 1993 Development paper.

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    Pavlopoulos Lab
    11/22/20 | Regionalized tissue fluidization by an actomyosin cable is required for epithelial gap closure during insect gastrulation.
    Jain A, Ulman V, Mukherjee A, Prakash M, Pimpale L, Munster S, Panfilio KA, Jug F, Grill SW, Tomancak P, Pavlopoulos A
    Nature Communications. 2020 Aug 22;11(1):5604. doi:

    Many animal embryos face early on in development the problem of having to pull and close an epithelial sheet around the spherical yolk-sac. During this gastrulation process, known as epiboly, the spherical geometry of the egg dictates that the epithelial sheet first expands and subsequently compacts to close around the sphere. While it is well recognized that contractile actomyosin cables can drive epiboly movements, it is unclear how pulling on the leading edge can lead to simultaneous tissue expansion and compaction. Moreover, the epithelial sheet spreading over the sphere is mechanically stressed and this stress needs to be dissipated for seamless closure. While oriented cell division is known to dissipate tissue stresses during epiboly, it is unclear how this can be achieved without cell division. Here we show that during extraembryonic tissue (serosa) epiboly in the red flour beetle Tribolium castaneum, the non-proliferative serosa becomes regionalized into two distinct territories: a dorsal region under higher tension away from the leading edge with larger, isodiametric and non-rearranging cells, and a more fluid ventral region under lower tension surrounding the leading edge with smaller, anisotropic cells undergoing cell intercalation. Our results suggest that fluidization of the leading edge is effected by a heterogeneous actomyosin cable that drives sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing in other systems, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.

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    Spruston LabMagee Lab
    11/22/12 | Synaptic amplification by dendritic spines enhances input cooperativity.
    Harnett MT, Makara JK, Spruston N, Kath WL, Magee JC
    Nature. 2012 Nov 22;491(7425):599-602. doi: 10.1038/nature11554

    Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (R(neck)) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that R(neck) is large enough ( 500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by  1.5- to  45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an R(neck)-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons.

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    Magee Lab
    11/21/12 | Hippocampal phase precession from dual input components.
    Chance FS
    The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012 Nov 21;32:16693-703a. doi: 10.1523/JNEUROSCI.2786-12.2012

    Phase precession is a well known phenomenon in which a hippocampal place cell will fire action potentials at successively earlier phases (relative to the theta-band oscillations recorded in the local field potential) as an animal moves through the cell’s receptive field (also known as a place field). We present a model in which CA1 pyramidal cell spiking is driven by dual input components arising from CA3 and EC3. The receptive fields of these two input components overlap but are offset in space from each other such that as the animal moves through the model place field, action potentials are driven first by the CA3 input component and then the EC3 input component. As CA3 synaptic input is known to arrive in CA1 at a later theta phase than EC3 input (Mizuseki et al., 2009; Montgomery et al., 2009), CA1 spiking advances in phase as the model transitions from CA3-driven spiking to EC3-driven spiking. Here spike phase is a function of animal location, placing our results in agreement with many experimental observations characterizing CA1 phase precession (O’Keefe and Recce, 1993; Huxter et al., 2003; Geisler et al., 2007). We predict that experimental manipulations that dramatically enhance or disrupt activity in either of these areas should have a significant effect on phase precession observed in CA1.

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    11/21/12 | Hippocampal pyramidal neurons comprise two distinct cell types that are countermodulated by metabotropic receptors.
    Graves AR, Moore SJ, Bloss EB, Mensh BD, Kath WL, Spruston N
    Neuron. 2012 Nov 21;76(4):776-89. doi: 10.1016/j.neuron.2012.09.036

    Relating the function of neuronal cell types to information processing and behavior is a central goal of neuroscience. In the hippocampus, pyramidal cells in CA1 and the subiculum process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information, which they transmit throughout the brain. Do these cells constitute a single class or are there multiple cell types with specialized functions? Using unbiased cluster analysis, we show that there are two morphologically and electrophysiologically distinct principal cell types that carry hippocampal output. We show further that these two cell types are inversely modulated by the synergistic action of glutamate and acetylcholine acting on metabotropic receptors that are central to hippocampal function. Combined with prior connectivity studies, our results support a model of hippocampal processing in which the two pyramidal cell types are predominantly segregated into two parallel pathways that process distinct modalities of information.

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