scholarly journals Distinct relations of microtubules and actin filaments with dendritic architecture

2019 ◽  
Author(s):  
Sumit Nanda ◽  
Shatabdi Bhattacharjee ◽  
Daniel N. Cox ◽  
Giorgio A. Ascoli
Keyword(s):  
Actin Filaments ◽  
Computational Simulation ◽  
Dendritic Morphology ◽  
Confocal Imaging ◽  
Dendritic Trees ◽  
Neural Tracing ◽  
Drosophila Larvae ◽  
Dendritic Branching ◽  
Molecular Patterns ◽  
Class Iv

SummaryMicrotubules and F-actin have long been recognized as key regulators of dendritic morphology. Nevertheless, precisely ascertaining their distinct influences on dendritic trees have been hampered until now by the lack of direct, arbor-wide cytoskeletal quantification. We pair live confocal imaging of fluorescently labeled dendritic arborization (da) neurons in Drosophila larvae with complete multi-signal neural tracing to separately measure microtubules and F-actin. We demonstrate that dendritic arbor length is highly interrelated with local microtubule quantity, whereas local F-actin enrichment is associated with dendritic branching. Computational simulation of arbor structure solely constrained by experimentally observed subcellular distributions of these cytoskeletal components generated synthetic morphological and molecular patterns statistically equivalent to those of real da neurons, corroborating the efficacy of local microtubule and F-actin in describing dendritic architecture. The analysis and modeling outcomes hold true for the simplest (Class I), most complex (Class IV), and genetically altered (Formin3 overexpression) da neuron types.SUPPORT: NIH R01 NS39600 and NS086082 and BICCN U01 MH114829.

scholarly journals TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression

2019 ◽  
Author(s):  
Josiah J. Herzog ◽  
Mugdha Deshpande ◽  
Weijin Xu ◽  
Reazur Rahman ◽  
Hannah Suib ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Dendritic Morphology ◽  
New Approach ◽  
Creb Activation ◽  
Dendritic Branching ◽  
Transcriptional Output ◽  
Dendritic Complexity ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein and forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, several neurological disorders display altered dendritic morphology and complexity, which are thought to precede neurodegeneration. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as a new approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescued defects in dendritic branching. Our data therefore provide a novel mechanism by which TDP-43 dysfunction interferes with dendritic branching, and define new pathways for therapeutic intervention in neurodegenerative diseases.

scholarly journals Helical buckling of actin inside filopodia generates traction

2014 ◽  
Vol 112 (1) ◽  
pp. 136-141 ◽  
Author(s):  
Natascha Leijnse ◽  
Lene B. Oddershede ◽  
Poul M. Bendix
Keyword(s):  
Cell Membrane ◽  
Rotational Motion ◽  
Actin Filaments ◽  
Cell Communication ◽  
Confocal Imaging ◽  
Actin Bundle ◽  
Cellular Processes ◽  
Membrane Protrusions ◽  
A Cell ◽  
Helical Buckling

Cells can interact with their surroundings via filopodia, which are membrane protrusions that extend beyond the cell body. Filopodia are essential during dynamic cellular processes like motility, invasion, and cell–cell communication. Filopodia contain cross-linked actin filaments, attached to the surrounding cell membrane via protein linkers such as integrins. These actin filaments are thought to play a pivotal role in force transduction, bending, and rotation. We investigated whether, and how, actin within filopodia is responsible for filopodia dynamics by conducting simultaneous force spectroscopy and confocal imaging of F-actin in membrane protrusions. The actin shaft was observed to periodically undergo helical coiling and rotational motion, which occurred simultaneously with retrograde movement of actin inside the filopodium. The cells were found to retract beads attached to the filopodial tip, and retraction was found to correlate with rotation and coiling of the actin shaft. These results suggest a previously unidentified mechanism by which a cell can use rotation of the filopodial actin shaft to induce coiling and hence axial shortening of the filopodial actin bundle.

scholarly journals CD14 is a coreceptor of Toll-like receptors 7 and 9

2010 ◽  
Vol 207 (12) ◽  
pp. 2689-2701 ◽  
Author(s):  
Christoph L. Baumann ◽  
Irene M. Aspalter ◽  
Omar Sharif ◽  
Andreas Pichlmair ◽  
Stephan Blüml ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Innate Immune ◽  
Confocal Imaging ◽  
Acid Uptake ◽  
Innate Immune Responses ◽  
Toll Like Receptors ◽  
Molecular Patterns ◽  
Cluster Of Differentiation

Recognition of pathogens by the innate immune system requires proteins that detect conserved molecular patterns. Nucleic acids are recognized by cytoplasmic sensors as well as by endosomal Toll-like receptors (TLRs). It has become evident that TLRs require additional proteins to be activated by their respective ligands. In this study, we show that CD14 (cluster of differentiation 14) constitutively interacts with the MyD88-dependent TLR7 and TLR9. CD14 was necessary for TLR7- and TLR9-dependent induction of proinflammatory cytokines in vitro and for TLR9-dependent innate immune responses in mice. CD14 associated with TLR9 stimulatory DNA in precipitation experiments and confocal imaging. The absence of CD14 led to reduced nucleic acid uptake in macrophages. Additionally, CD14 played a role in the stimulation of TLRs by viruses. Using various types of vesicular stomatitis virus, we showed that CD14 is dispensable for viral uptake but is required for the triggering of TLR-dependent cytokine responses. These data show that CD14 has a dual role in nucleic acid–mediated TLR activation: it promotes the selective uptake of nucleic acids, and it acts as a coreceptor for endosomal TLR activation.

scholarly journals Wide-field ganglion cells in macaque retinas

2005 ◽  
Vol 22 (4) ◽  
pp. 383-393 ◽  
Author(s):  
ELIZABETH S. YAMADA ◽  
ANDREA S. BORDT ◽  
DAVID W. MARSHAK
Keyword(s):  
Ganglion Cells ◽  
Plexiform Layer ◽  
Cell Types ◽  
Wide Field ◽  
Inner Plexiform Layer ◽  
Branching Pattern ◽  
Dendritic Trees ◽  
Dendritic Branching ◽  
Bistratified Cell

To describe the wide-field ganglion cells, they were injected intracellularly with Neurobiotin using an in vitro preparation of macaque retina and labeled with streptavidin-Cy3. The retinas were then labeled with antibodies to choline acetyltransferase and other markers to indicate the depth of the dendrites within the inner plexiform layer (IPL) and analyzed by confocal microscopy. There were eight different subtypes of narrowly unistratified cells that ramified in each of the 5 strata, S1–5, including narrow thorny, large sparse, large moderate, large dense, large radiate, narrow wavy, large very sparse, and fine very sparse. There were four types of broadly stratified cells with dendritic trees extending from S4 to S2. One type resembled the parvocellular giant cell and another the broad thorny type described previously in primates. Another broadly stratified cell was called multi-tufted based on its distinctive dendritic branching pattern. The fourth type had been described previously, but not named; we called it broad wavy. There was a bistratified type with its major arbor in S5, the same level as the blue cone bipolar cell; it resembled the large, bistratified cell with blue ON-yellow OFF responses described recently. Two wide-field ganglion cell types were classified as diffuse because they had dendrites throughout the IPL. One had many small branches and was named thorny diffuse. The second was named smooth diffuse because it had straighter dendrites that lacked these processes. Dendrites of the large moderate and multi-tufted cells cofasciculated with ON-starburst cell dendrites and were, therefore, candidates to be ON- and ON–OFF direction-selective ganglion cells, respectively. We concluded that there are at least 15 morphoplogical types of wide-field ganglion cells in macaque retinas.

scholarly journals Neuronal processing of noxious thermal stimuli mediated by dendritic Ca2+ influx in Drosophila somatosensory neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Shin-Ichiro Terada ◽  
Daisuke Matsubara ◽  
Koun Onodera ◽  
Masanori Matsuzaki ◽  
Tadashi Uemura ◽  
...  
Keyword(s):  
High Frequency ◽  
Light Stimulation ◽  
Avoidance Behaviors ◽  
Drosophila Larvae ◽  
Somatosensory Neurons ◽  
Signal Encoding ◽  
Tissue Damages ◽  
Neuronal Processing ◽  
Thermal Stimuli ◽  
Class Iv

Adequate responses to noxious stimuli causing tissue damages are essential for organismal survival. Class IV neurons in Drosophila larvae are polymodal nociceptors responsible for thermal, mechanical, and light sensation. Importantly, activation of Class IV provoked distinct avoidance behaviors, depending on the inputs. We found that noxious thermal stimuli, but not blue light stimulation, caused a unique pattern of Class IV, which were composed of pauses after high-frequency spike trains and a large Ca2+ rise in the dendrite (the Ca2+ transient). Both these responses depended on two TRPA channels and the L-type voltage-gated calcium channel (L-VGCC), showing that the thermosensation provokes Ca2+ influx. The precipitous fluctuation of firing rate in Class IV neurons enhanced the robust heat avoidance. We hypothesize that the Ca2+ influx can be a key signal encoding a specific modality.

scholarly journals Salt-Mediated Stiffening, Destruction, and Resculpting of Actomyosin Network

2021 ◽  
Vol 9 ◽  
Author(s):  
Bekele J. Gurmessa ◽  
Michael J. Rust ◽  
Moumita Das ◽  
Jennifer L. Ross ◽  
Rae M. Robertson-Anderson
Keyword(s):  
Optical Tweezers ◽  
Actin Filaments ◽  
Viscoelastic Properties ◽  
Structural Changes ◽  
Myosin Ii ◽  
Structural Evolution ◽  
Confocal Imaging ◽  
Actin Binding ◽  
Time Varying ◽  
High Concentrations

Cells dynamically change their viscoelastic properties by restructuring networks of actin filaments in the cytoskeleton, enabling diverse mechanical processes such as mobility and apoptosis. This restructuring is modulated, in part, by actin-binding proteins, such as myosin II, as well as counterions such as Mg2+ and K+. While high concentrations of Mg2+ can induce bundling and crosslinking of actin filaments, high concentrations of K+ destabilize myosin II minifilaments necessary to crosslink actin filaments. Here, we elucidate how the mechanics and structure of actomyosin networks evolve under competing effects of varying Mg2+ and K+ concentrations. Specifically, we couple microfluidics with optical tweezers microrheology to measure the time-varying linear viscoelastic moduli of actin networks crosslinked via myosin II as we cycle between low and high Mg2+ and K+ concentrations. Our complementary confocal imaging experiments correlate the time-varying viscoelastic properties with salt-mediated structural evolution. We find that the elastic modulus displays an intriguing non-monotonic time dependence in high-salt conditions, that correlates with structural changes, and that this process is irreversible, with the network evolving to a new steady-state as Mg2+ and K+ decrease back to their initial concentrations.

scholarly journals Effects of exercise training on dendritic morphology in the cardiorespiratory and locomotor centers of the mature rat brain

2010 ◽  
Vol 108 (6) ◽  
pp. 1582-1590 ◽  
Author(s):  
Amanda J. Nelson ◽  
Janice M. Juraska ◽  
Brian G. Ragan ◽  
Gary A. Iwamoto
Keyword(s):  
Exercise Training ◽  
Rat Brain ◽  
Dendritic Morphology ◽  
Ventrolateral Medulla ◽  
Heart Weight ◽  
Activity Levels ◽  
Sprague Dawley ◽  
Hypothalamic Area ◽  
Early Postnatal Development ◽  
Dendritic Branching

It has been shown that dendritic branching in neural cardiorespiratory and locomotor centers can be attenuated with exercise training (ET) initiated immediately after weaning. The purpose of this study was to determine whether neuroplastic changes occur within cardiorespiratory and locomotor centers due to ET after maturation. Male Sprague-Dawley rats (21 days old, n = 28) were individually housed in standard cages. At 91 days of age, animals were divided into two groups: untrained (UN; n = 14) and trained (TR; n = 14). The TR group exercised spontaneously for 50 days on running wheels. ET indexes were obtained, including maximal O2 consumption, percent body fat, resting heart rate, and heart weight-to-body weight ratios. The brain was processed with a modified Golgi-Cox procedure. Impregnated neurons from the periaqueductal gray (PAG), posterior hypothalamic area (PH), nucleus of the tractus solitarius (NTS), cuneiform nucleus (CnF), rostral ventrolateral medulla, nucleus cuneatus, and cerebral cortex were examined. Neurons were traced and analyzed using the Sholl concentric ring analysis of dendritic branching. The mean total number of dendritic intersections with the concentric rings per neuron per animal were compared between UN and TR groups. There were significant differences between UN and TR groups in the PH, PAG, CnF, and NTS in the total number of intersections per animal. In some areas, the effect size was smaller when ET was initiated in mature animals, possibly related to their relatively reduced activity levels. In conclusion, the adult rat brain remains dynamic and adapts to chronic ET. However, some brain areas appear to be more affected if ET is initiated in early postnatal development.

Morphology of wide-field bistratified and diffuse human retinal ganglion cells

2000 ◽  
Vol 17 (4) ◽  
pp. 567-578 ◽  
Author(s):  
BETH B. PETERSON ◽  
DENNIS M. DACEY
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Field Size ◽  
Wide Field ◽  
Human Retina ◽  
Retinal Ganglion ◽  
Branch Points ◽  
Dendritic Trees ◽  
Dendritic Field ◽  
Dendritic Branching

To study the detailed morphology of human retinal ganglion cells, we used intracellular injection of horseradish peroxidase and Neurobiotin to label over 1000 cells in an in vitro, wholemount preparation of the human retina. This study reports on the morphology of 119 wide-field bistratified and 42 diffuse ganglion cells. Cells were analyzed quantitatively on the basis of dendritic-field size, soma size, and the extent of dendritic branching. Bistratified cells were similar in dendritic-field diameter (mean ± s.d. = 682 ± 130 μm) and soma diameter (mean ± s.d. = 18 ± 3.3 μm) but showed a broad distribution in the extent of dendritic branching (mean ± s.d. branch point number = 67 ± 32; range = 15–167). Differences in the extent of branching and in dendritic morphology and the pattern of branching suggest that the human retina may contain at least three types of wide-field bistratified cells. Diffuse ganglion cells comprised a largely homogeneous group whose dendrites ramified throughout the inner plexiform layer. The diffuse cells had similar dendritic-field diameters (mean ± s.d. = 486 ± 113 μm), soma diameters (mean ± s.d. = 16 ± 2.3 μm), and branch points numbers (mean ± s.d. = 92 ± 32). The majority had densely branched dendritic trees and thin, very spiny dendrites with many short, fine, twig-like thorny processes. Five of the diffuse cells had much more sparsely branched dendritic trees (<50 branch points) and less spiny dendrites, suggesting that there are possibly two types of diffuse ganglion cells in human retina. Although the presence of a diversity of large bistratified and diffuse ganglion cells has been observed in a variety of mammalian retinas, little is known about the number of cell types, their physiological properties, or their central projections. Some of the human wide-field bistratified cells in the present study, however, show morphological similarities to monkey large bistratified cells that are known to project to the superior colliculus.

Live Neuron Morphology Automatically Reconstructed From Multiphoton and Confocal Imaging Data

2008 ◽  
Vol 100 (4) ◽  
pp. 2422-2429 ◽  
Author(s):  
Bradley E. Losavio ◽  
Yong Liang ◽  
Alberto Santamaría-Pang ◽  
Ioannis A. Kakadiaris ◽  
Costa M. Colbert ◽  
...  
Keyword(s):  
Background Noise ◽  
Laser Scanning ◽  
Three Dimensional ◽  
Dendritic Morphology ◽  
Confocal Imaging ◽  
Laser Scanning Microscopy ◽  
Imaging Data ◽  
Neuron Morphology ◽  
Software Suite ◽  
Experimental Conditions

We have developed a fully automated procedure for extracting dendritic morphology from multiple three-dimensional image stacks produced by laser scanning microscopy. By eliminating human intervention, we ensure that the results are objective, quickly generated, and accurate. The software suite accounts for typical experimental conditions by reducing background noise, removing pipette artifacts, and aligning multiple overlapping image stacks. The output morphology is appropriate for simulation in compartmental simulation environments. In this report, we validate the utility of this procedure by comparing its performance on live neurons and test specimens with other fully and semiautomated reconstruction tools.

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