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Automated spatio-temporal analysis of dendritic spines and related protein dynamics

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  • Vincent On
  • Atena Zahedi
  • Iryna M Ethell
  • Bir Bhanu

Abstract

Cofilin and other Actin-regulating proteins are essential in regulating the shape of dendritic spines, which are sites of neuronal communications in the brain, and their malfunctions are implicated in neurodegeneration related to aging. The analysis of cofilin motility in dendritic spines using fluorescence video-microscopy may allow for the discovery of its effects on synaptic functions. To date, the flow of cofilin has not been analyzed by automatic means. This paper presents Dendrite Protein Analysis (DendritePA), a novel automated pattern recognition software to analyze protein trafficking in neurons. Using spatiotemporal information present in multichannel fluorescence videos, the DendritePA generates a temporal maximum intensity projection that enhances the signal-to-noise ratio of important biological structures, segments and tracks dendritic spines, estimates the density of proteins in spines, and analyzes the flux of proteins through the dendrite/spine boundary. The motion of a dendritic spine is used to generate spine energy images, which are used to automatically classify the shape of common dendritic spines such as stubby, mushroom, or thin. By tracking dendritic spines over time and using their intensity profiles, the system can analyze the flux patterns of cofilin and other fluorescently stained proteins. The cofilin flux patterns are found to correlate with the dynamic changes in dendritic spine shapes. Our results also have shown that the activation of cofilin using genetic manipulations leads to immature spines while its inhibition results in an increase in mature spines.

Suggested Citation

  • Vincent On & Atena Zahedi & Iryna M Ethell & Bir Bhanu, 2017. "Automated spatio-temporal analysis of dendritic spines and related protein dynamics," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-23, August.
    • Handle: RePEc:plo:pone00:0182958
    DOI: 10.1371/journal.pone.0182958
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    References listed on IDEAS

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    1. Silvia Arber & Freda A. Barbayannis & Hartwig Hanser & Corinna Schneider & Clement A. Stanyon & Ora Bernard & Pico Caroni, 1998. "Regulation of actin dynamics through phosphorylation of cofilin by LIM-kinase," Nature, Nature, vol. 393(6687), pages 805-809, June.
    2. Alfredo Rodriguez & Douglas B Ehlenberger & Dara L Dickstein & Patrick R Hof & Susan L Wearne, 2008. "Automated Three-Dimensional Detection and Shape Classification of Dendritic Spines from Fluorescence Microscopy Images," PLOS ONE, Public Library of Science, vol. 3(4), pages 1-12, April.
    3. Mathew E Berginski & Eric A Vitriol & Klaus M Hahn & Shawn M Gomez, 2011. "High-Resolution Quantification of Focal Adhesion Spatiotemporal Dynamics in Living Cells," PLOS ONE, Public Library of Science, vol. 6(7), pages 1-13, July.
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