Main Menu (Mobile)- Block

Main Menu - Block

custom | custom

Search Results

filters_region_cap | custom

Filter

facetapi-Q2b17qCsTdECvJIqZJgYMaGsr8vANl1n | block

Associated Lab

facetapi-W9JlIB1X0bjs93n1Alu3wHJQTTgDCBGe | block
facetapi-61yz1V0li8B1bixrCWxdAe2aYiEXdhd0 | block
facetapi-PV5lg7xuz68EAY8eakJzrcmwtdGEnxR0 | block
general_search_page-panel_pane_1 | views_panes

1457 Janelia Publications

Showing 1-10 of 1457 results
12/03/18 | Developmental pattern and structural factors of dendritic survival in cerebellar granule cells in vivo.
Dhar M, Hantman AW, Nishiyama H
Scientific Reports. 2018 Dec 03;8(1):17561. doi: 10.1038/s41598-018-35829-y

Granule cells (GCs) in the cerebellar cortex are important for sparse encoding of afferent sensorimotor information. Modeling studies show that GCs can perform their function most effectively when they have four dendrites. Indeed, mature GCs have four short dendrites on average, each terminating in a claw-like ending that receives both excitatory and inhibitory inputs. Immature GCs, however, have significantly more dendrites-all without claws. How these redundant dendrites are refined during development is largely unclear. Here, we used in vivo time-lapse imaging and immunohistochemistry to study developmental refinement of GC dendritic arbors and its relation to synapse formation. We found that while the formation of dendritic claws stabilized the dendrites, the selection of surviving dendrites was made before claw formation, and longer immature dendrites had a significantly higher chance of survival than shorter dendrites. Using immunohistochemistry, we show that glutamatergic and GABAergic synapses are transiently formed on immature GC dendrites, and the number of GABAergic, but not glutamatergic, synapses correlates with the length of immature dendrites. Together, these results suggest a potential role of transient GABAergic synapses on dendritic selection and show that preselected dendrites are stabilized by the formation of dendritic claws-the site of mature synapses.

View Publication Page
11/30/18 | Brain-wide circuit interrogation at the cellular level guided by online analysis of neuronal function.
Vladimirov N, Wang C, Höckendorf B, Pujala A, Tanimoto M, Mu Y, Yang C, Wittenbach J, Freeman J, Preibisch S, Koyama M, Keller PJ, Ahrens MB
Nature Methods. 2018 Nov 30;15(12):1117-1125. doi: 10.1038/s41592-018-0221-x

Whole-brain imaging allows for comprehensive functional mapping of distributed neural pathways, but neuronal perturbation experiments are usually limited to targeting predefined regions or genetically identifiable cell types. To complement whole-brain measures of activity with brain-wide manipulations for testing causal interactions, we introduce a system that uses measuredactivity patterns to guide optical perturbations of any subset of neurons in the same fictively behaving larval zebrafish. First, a light-sheet microscope collects whole-brain data that are rapidly analyzed by a distributed computing system to generate functional brain maps. On the basis of these maps, the experimenter can then optically ablate neurons and image activity changes across the brain. We applied this method to characterize contributions of behaviorally tuned populations to the optomotor response. We extended the system to optogenetically stimulate arbitrary subsets of neurons during whole-brain imaging. These open-source methods enable delineating the contributions of neurons to brain-wide circuit dynamics and behavior in individual animals.

View Publication Page
11/12/18 | Neuron-subtype-specific expression, interaction affinities, and specificity determinants of DIP/Dpr cell recognition proteins.
Cosmanescu F, Katsamba PS, Sergeeva AP, Ahlsen G, Patel SD, Brewer JJ, Tan L, Xu S, Xiao Q, Nagarkar-Jaiswal S, Nern A, Bellen HJ, Zipursky SL, Honig B, Shapiro L
Neuron. 2018 Nov 12:. doi: 10.1016/j.neuron.2018.10.046

Binding between DIP and Dpr neuronal recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in vivo.

View Publication Page
11/29/18 | Analysis of discrete local variability and structural covariance in macromolecular assemblies using Cryo-EM and focused classification.
Zhang C, Cantara W, Jeon Y, Musier-Forsyth K, Grigorieff N, Lyumkis D
Ultramicroscopy. 2018 Nov 29:. doi: 10.1016/j.ultramic.2018.11.016

Single-particle electron cryo-microscopy and computational image classification can be used to analyze structural variability in macromolecules and their assemblies. In some cases, a particle may contain different regions that each display a range of distinct conformations. We have developed strategies, implemented within the Frealign and cisTEM image processing packages, to focus classify on specific regions of a particle and detect potential covariance. The strategies are based on masking the region of interest using either a 2-D mask applied to reference projections and particle images, or a 3-D mask applied to the 3-D volume. We show that focused classification approaches can be used to study structural covariance, a concept that is likely to gain more importance as datasets grow in size, allowing the distinction of more structural states and smaller differences between states. Finally, we apply the approaches to an experimental dataset containing the HIV-1 Transactivation Response (TAR) element RNA fused into the large bacterial ribosomal subunit to deconvolve structural mobility within localized regions of interest, and to a dataset containing assembly intermediates of the large subunit to measure structural covariance.

View Publication Page
11/27/18 | Temporal control of Drosophila central nervous system development.
Miyares RL, Lee T
Current Opinion in Neurobiology. 2018 Nov 27;56:24-32. doi: 10.1016/j.conb.2018.10.016

A complex nervous system requires precise numbers of various neuronal types produced with exquisite spatiotemporal control. This striking diversity is generated by a limited number of neural stem cells (NSC), where spatial and temporal patterning intersect. Drosophila is a genetically tractable model system that has significant advantages for studying stem cell biology and neuronal fate specification. Here we review the latest findings in the rich literature of temporal patterning of neuronal identity in the Drosophila central nervous system. Rapidly changing consecutive transcription factors expressed in NSCs specify short series of neurons with considerable differences. More slowly progressing changes are orchestrated by NSC intrinsic temporal factor gradients which integrate extrinsic signals to coordinate nervous system and organismal development.

View Publication Page
11/25/18 | Magnetocaloric materials as switchable high contrast ratio MRI labels.
Barbic M, Dodd SJ, Morris HD, Dilley N, Marcheschi B, Huston A, Harris TD, Koretsky AP
Magnetic Resonance in Medicine. 2018 Nov 25:. doi: 10.1002/mrm.27615

PURPOSE: To develop switchable and tunable labels with high contrast ratio for MRI using magnetocaloric materials that have sharp first-order magnetic phase transitions at physiological temperatures and typical MRI magnetic field strengths.

METHODS: A prototypical magnetocaloric material iron-rhodium (FeRh) was prepared by melt mixing, high-temperature annealing, and ice-water quenching. Temperature- and magnetic field-dependent magnetization measurements of wire-cut FeRh samples were performed on a vibrating sample magnetometer. Temperature-dependent MRI of FeRh samples was performed on a 4.7T MRI.

RESULTS: Temperature-dependent MRI clearly demonstrated image contrast changes due to the sharp magnetic state transition of the FeRh samples in the MRI magnetic field (4.7T) and at a physiologically relevant temperature (~37°C).

CONCLUSION: A magnetocaloric material, FeRh, was demonstrated to act as a high contrast ratio switchable MRI contrast agent due to its sharp first-order magnetic phase transition in the DC magnetic field of MRI and at physiologically relevant temperatures. A wide range of magnetocaloric materials are available that can be tuned by materials science techniques to optimize their response under MRI-appropriate conditions and be controllably switched in situ with temperature, magnetic field, or a combination of both.

View Publication Page
11/23/18 | Paring down to the essentials.
Wang T
Science (New York, N.Y.). 2018 Nov 23;362(6417):904. doi: 10.1126/science.aav6872
11/22/18 | Sensorimotor pathway controlling stopping behavior during chemotaxis in the larva.
Tastekin I, Khandelwal A, Tadres D, Fessner ND, Truman JW, Zlatic M, Cardona A, Louis M
eLife. 2018 Nov 22;7:. doi: 10.7554/eLife.38740

Sensory navigation results from coordinated transitions between distinct behavioral programs. During chemotaxis in the larva, the detection of positive odor gradients extends runs while negative gradients promote stops and turns. This algorithm represents a foundation for the control of sensory navigation across phyla. In the present work, we identified an olfactory descending neuron, PDM-DN, which plays a pivotal role in the organization of stops and turns in response to the detection of graded changes in odor concentrations. Artificial activation of this descending neuron induces deterministic stops followed by the initiation of turning maneuvers through head casts. Using electron microscopy, we reconstructed the main pathway that connects the PDM-DN neuron to the peripheral olfactory system and to the pre-motor circuit responsible for the actuation of forward peristalsis. Our results set the stage for a detailed mechanistic analysis of the sensorimotor conversion of graded olfactory inputs into action selection to perform goal-oriented navigation.

View Publication Page
11/21/18 | Brain-wide organization of neuronal activity and convergent sensorimotor transformations in larval zebrafish.
Chen X, Mu Y, Hu Y, Kuan AT, Nikitchenko M, Randlett O, Chen AB, Gavornik JP, Sompolinsky H, Engert F, Ahrens MB
Neuron. 2018 Nov 21;100(4):876-890.e5. doi: 10.1016/j.neuron.2018.09.042

Simultaneous recordings of large populations of neurons in behaving animals allow detailed observation of high-dimensional, complex brain activity. However, experimental approaches often focus on singular behavioral paradigms or brain areas. Here, we recorded whole-brain neuronal activity of larval zebrafish presented with a battery of visual stimuli while recording fictive motor output. We identified neurons tuned to each stimulus type and motor output and discovered groups of neurons in the anterior hindbrain that respond to different stimuli eliciting similar behavioral responses. These convergent sensorimotor representations were only weakly correlated to instantaneous motor activity, suggesting that they critically inform, but do not directly generate, behavioral choices. To catalog brain-wide activity beyond explicit sensorimotor processing, we developed an unsupervised clustering technique that organizes neurons into functional groups. These analyses enabled a broad overview of the functional organization of the brain and revealed numerous brain nuclei whose neurons exhibit concerted activity patterns.

View Publication Page
11/15/18 | Visualizing intracellular organelle and cytoskeletal interactions at nanoscale resolution on millisecond timescales.
Guo Y, Li D, Zhang S, Yang Y, Liu J, Wang X, Liu C, Milkie DE, Moore RP, Tulu US, Kiehart DP, Hu J, Lippincott-Schwartz J, Betzig E, Li D
Cell. 2018 Nov 15;175(5):1430-42. doi: 10.1016/j.cell.2018.09.057

In eukaryotic cells, organelles and the cytoskeleton undergo highly dynamic yet organized interactions capable of orchestrating complex cellular functions. Visualizing these interactions requires noninvasive, long-duration imaging of the intracellular environment at high spatiotemporal resolution and low background. To achieve these normally opposing goals, we developed grazing incidence structured illumination microscopy (GI-SIM) that is capable of imaging dynamic events near the basal cell cortex at 97-nm resolution and 266 frames/s over thousands of time points. We employed multi-color GI-SIM to characterize the fast dynamic interactions of diverse organelles and the cytoskeleton, shedding new light on the complex behaviors of these structures. Precise measurements of microtubule growth or shrinkage events helped distinguish among models of microtubule dynamic instability. Analysis of endoplasmic reticulum (ER) interactions with other organelles or microtubules uncovered new ER remodeling mechanisms, such as hitchhiking of the ER on motile organelles. Finally, ER-mitochondria contact sites were found to promote both mitochondrial fission and fusion.

View Publication Page