Introduction to connectomics

Spring 2016

Th 1:30-4:30pm

Location: A59 Neuroscience Institute

Survey of contemporary techniques in computational neuroanatomy. Brain imaging via light and electron microscopy; computer vision, graphics, machine learning, and crowdsourcing for neural circuit reconstruction; graph layout, spectral methods, and latent variable models for connectome analysis; applications to C. elegans, fly, retina, and cortex.

Prerequisites

• basics of linear algebra, multivariate calculus, algorithms and data structures
• command of a programming language
• knowledge of computer vision, machine learning, and neuroscience will be helpful
• undergraduates by permission of the instructor

Class requirements

• reading research papers
• class participation
• final project

Lecture Schedule

• Feb. 4. Introduction and overview.
  • Target readings
    • Lichtman, Jeff W., and Winfried Denk. “The big and the small: challenges of imaging the brain’s circuits.” Science 334.6056 (2011): 618-623.
    • Bargmann, Cornelia I., and Eve Marder. “From the connectome to brain function.” Nature methods 10.6 (2013): 483-490.
  • Background readings
    • Seung, Sebastian. Connectome: How the brain’s wiring makes us who we are. Houghton Mifflin Harcourt, 2012.
    • Bargmann, Cornelia, et al. “BRAIN 2025: a scientific vision.” Brain Research through Advancing Neurotechnologies (BRAIN) Working Group Report to the Advisory Committee to the Director. National Institutes of Health, Bethesda (2014).
    • Gilbert, Mads, et al. “Resuscitation from accidental hypothermia of 13· 7 C with circulatory arrest.” The Lancet 355.9201 (2000): 375-376.
• Feb. 11. Fixation, staining, embedding.
  • Target readings
    • Tapia, Juan Carlos, et al. “High-contrast en bloc staining of neuronal tissue for field emission scanning electron microscopy.” Nature protocols 7.2 (2012): 193-206.
    • Hua, Y., P. Laserstein, and M. Helmstaedter. “Large-volume en-bloc staining for electron microscopy-based connectomics.” Nature communications 6 (2015): 7923.
    • Martell, Jeffrey D., et al. “Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy.” Nature biotechnology 30.11 (2012): 1143-1148.
  • Background readings
    • Kuwajima, M. and K. Harris. Cross-linking fixatives: What they are, what they do, and why we use them.
    • Kiernan, J. A. Formaldehyde, formalin, paraformaldehyde and glutaraldehyde: What they are and what they do.
    • Pandithage, R. Brief Introduction to Contrasting for EM Sample Preparation.
    • Korogod, Natalya, Carl CH Petersen, and Graham W. Knott. “Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation.” Elife 4 (2015): e05793.
    • Mikula, Shawn, and Winfried Denk. “High-resolution whole-brain staining for electron microscopic circuit reconstruction.” Nature Methods 12.6 (2015): 541-546.
• Feb. 18. Microtomy and microscopy.
  • Target readings
    • Briggman, Kevin L., and Davi D. Bock. “Volume electron microscopy for neuronal circuit reconstruction.” Current opinion in neurobiology 22.1 (2012): 154-161.
    • Hayworth, Kenneth J., et al. “Imaging ATUM ultrathin section libraries with WaferMapper: a multi-scale approach to EM reconstruction of neural circuits.” Frontiers in Neural Circuits 8 (2014): 68.
    • Hayworth, Kenneth J., et al. “Ultrastructurally smooth thick partitioning and volume stitching for large-scale connectomics.” Nature methods 12.4 (2015): 319-322.
  • Background readings
    • Harris, Kristen M., et al. “Uniform serial sectioning for transmission electron microscopy.” The Journal of neuroscience 26.47 (2006): 12101-12103. See also Supplemental Movies.
    • Feynman, Richard Phillips, Robert B. Leighton, and Matthew Sands. “The Motion of Charges in Electric and Magnetic Fields.”  The Feynman lectures on physics, vol. 2: Mainly electromagnetism and matter. Addison-Wesley, 1979.
• Feb. 25. Image assembly.
  • Target readings
    • Saalfeld, Stephan, et al. “As-rigid-as-possible mosaicking and serial section registration of large ssTEM datasets.” Bioinformatics 26.12 (2010): i57-i63.
    • Saalfeld, Stephan, et al. “Elastic volume reconstruction from series of ultra-thin microscopy sections.” Nature Methods 9.7 (2012): 717-720.
  • Background readings
    • Lewis, J. P. “Fast normalized cross-correlation.” Vision interface. Vol. 10. No. 1. 1995.
• Mar. 3. Convolutional networks.
  • Turaga, Srinivas C., et al. “Convolutional networks can learn to generate affinity graphs for image segmentation.” Neural computation 22.2 (2010): 511-538.
  • Lee, Kisuk, et al. “Recursive Training of 2D-3D Convolutional Networks for Neuronal Boundary Prediction.” Advances in Neural Information Processing Systems. 2015.
• Mar. 10. Agglomerative clustering.
  • Jain, Viren, et al. “Learning to agglomerate superpixel hierarchies.” Advances in Neural Information Processing Systems. 2011.
• Mar. 24. Human-computer interaction.
  • Cardona, Albert, et al. “TrakEM2 software for neural circuit reconstruction.”PloS one 7.6 (2012): e38011.
  • Helmstaedter, Moritz, Kevin L. Briggman, and Winfried Denk. “High-accuracy neurite reconstruction for high-throughput neuroanatomy.” Nature neuroscience 14.8 (2011): 1081-1088.
• Mar. 31. Social computing.  Crowd wisdom, gamification, and community.
  • Saalfeld, Stephan, et al. “CATMAID: collaborative annotation toolkit for massive amounts of image data.” Bioinformatics 25.15 (2009): 1984-1986.
  • Helmstaedter, Moritz, Kevin L. Briggman, and Winfried Denk. “High-accuracy neurite reconstruction for high-throughput neuroanatomy.” Nature neuroscience 14.8 (2011): 1081-1088.
  • Kim, Jinseop S., et al. “Space-time wiring specificity supports direction selectivity in the retina.” Nature 509.7500 (2014): 331.
• Apr. 7. C. elegans. Graph layout and spectral methods. Wiring length minimization.
  • Target readings
    • Varshney, Lav R., et al. “Structural properties of the Caenorhabditis elegans neuronal network.” PLoS Comput Biol 7.2 (2011): e1001066.
    • Chen, Beth L., David H. Hall, and Dmitri B. Chklovskii. “Wiring optimization can relate neuronal structure and function.” Proceedings of the National Academy of Sciences of the United States of America 103.12 (2006): 4723-4728.
  • Background readings
    • White, J. G., et al. “The structure of the nervous system of the nematode Caenorhabditis elegans: the mind of a worm.” Phil. Trans. R. Soc. Lond 314 (1986): 1-340.
• Apr. 14. Fly.
  • Takemura, Shin-ya, et al. “A visual motion detection circuit suggested by Drosophila connectomics.” Nature 500.7461 (2013): 175-181.
  • Background reading
    • Clifford, Colin WG, and M. R. Ibbotson. “Fundamental mechanisms of visual motion detection: models, cells and functions.” Progress in neurobiology 68.6 (2002): 409-437.
• Apr. 21. Retina.
  • Briggman, Kevin L., Moritz Helmstaedter, and Winfried Denk. “Wiring specificity in the direction-selectivity circuit of the retina.” Nature 471.7337 (2011): 183-188.
  • Kim, Jinseop S., et al. “Space-time wiring specificity supports direction selectivity in the retina.” Nature 509.7500 (2014): 331.
• Apr. 28. Cortex.
  • Target readings
    • Lee, Wei-Chung Allen, Vincent Bonin, Michael Reed, Brett J. Graham, Greg Hood, Katie Glattfelder, and R. Clay Reid. “Anatomy and function of an excitatory network in the visual cortex.” Nature 532: 370-374 (2016).
  • Background reading
    • Cossell, L., et al. “Functional organization of excitatory synaptic strength in primary visual cortex.” Nature 518.7539 (2015): 399.