EPBscore: a Novel Method for Computer-Assisted Analysis of Axonal Structure and Dynamics
- 630 Downloads
Live brain imaging at cellular and synaptic resolution has dramatically improved our understanding of its organization and plasticity. A major issue in this field is the lack of automated tools to reliably analyze synaptic structures without heavily depending on the user’s subjectivity. As time-lapse imaging experiments can produce vast amounts of data, the tediousness of extracting key structural features of neurites such as the number, location and size of synaptic contacts through image analysis is a major bottleneck to perform large-scale studies. Unbiased quantitative tracking of large populations of synaptic sites is still challenging (Helmstaedter et al. 2011), despite the importance of understanding the principles of synaptic organization, connectivity and plasticity. This task is especially complex for axons and their boutons (Brown et al. 2011). Canonical cortical axons have a relatively simple structure, consisting of thin axonal shafts with uniform diameters (~100–1000 nm,...
KeywordsAxons Axonal boutons Automated analysis Segmentation Synaptic plasticity Learning and memory Aging Presynaptic Connectivity In vivo 2-photon imaging
We thank Karel Svoboda for support and for critical input on the initial development of EPBscore. Anthony Holtmaat, Linda Wilbrecht for help with an initial set of experiments. Lucien West, Jonathan Bowen, Dawn Thompson, Graham Little for help with the analysis. Cher Bachar for help with Matlab implementation. SS is supported by grants from NSFC (91332122 and 31171047), and a seed grant from the Center for Brain-inspired Computation Research. This work was funded by the Medical Research Council, UK.
- Brown, K. M., Barrionuevo, G., Canty, A. J., De Paola, V., Hirsch, J. A., Jefferis, G. S., Lu, J., Snippe, M., Sugihara, I., & Ascoli, G. A. (2011). The DIADEM data sets: representative light microscopy images of neuronal morphology to advance automation of digital reconstructions. Neuroinformatics, 9, 143–157.PubMedPubMedCentralCrossRefGoogle Scholar
- Canty, A. J., Teles-Grilo Ruivo, L. M., Nesarajah, C., Song, S., Jackson, J. S., Little, G. E., & De Paola, V. (2013b). Synaptic elimination and protection after minimal injury depend on cell type and their prelesion structural dynamics in the adult cerebral cortex. Journal of Neuroscience, 33, 10374–10383.PubMedCrossRefGoogle Scholar
- Grillo, F. W., Song, S., Teles-Grilo Ruivo, L. M., Huang, L., Gao, G., Knott, G. W., Maco, B., Ferretti, V., Thompson, D., Little, G. E., et al. (2013). Increased axonal bouton dynamics in the aging mouse cortex. Proceedings of the National Academy of Sciences of the United States of America, 110, E1514–E1523.PubMedPubMedCentralCrossRefGoogle Scholar
- Holtmaat, A., Bonhoeffer, T., Chow, D. K., Chuckowree, J., De Paola, V., Hofer, S. B., Hubener, M., Keck, T., Knott, G., Lee, W. C., et al. (2009). Long-term, High-Resolution imaging in the mouse neocortex through a chronic cranial window. Nature Protocols, 4, 1128–1144.PubMedPubMedCentralCrossRefGoogle Scholar
- Liebscher, S., Page, R. M., Kafer, K., Winkler, E., Quinn, K., Goldbach, E., Brigham, E. F., Quincy, D., Basi, G. S., Schenk, D. B., et al. (2013). Chronic Gamma-Secretase inhibition reduces amyloid Plaque-Associated instability of Pre- and postsynaptic structures. Molecular Psychiatry, 19, 937–946.PubMedPubMedCentralCrossRefGoogle Scholar
- Tsai, P.S., Nishimura, N., Yoder, E.J., White, A., Dolnick E., and Kleinfeld, D. (2002). Principles, design, and construction of a two photon laser scanning microscope for in vitro and in vivo brain imaging. In Methods for In Vivo Optical Imaging (R. Frostig, editor), 2002, CRC Press, pp. 113–171.Google Scholar
- Wilson, C. S. (1984). Theory and practice of scanning optical microscopy. New York: Academic.Google Scholar