9.912/MCB 206 Introduction to Connectomics

http://hebb.mit.edu/courses/connectomics/
Graduate seminar class at MIT and Harvard, Fall 2007
Organizers: Sebastian Seung (seung@mit.edu), Jeff Lichtman (jeff@mcb.harvard.edu), and Clay Reid (clay_reid@hms.harvard.edu)
Units: 3-0-6
Prereq: Basic knowledge of neuroscience (undergraduates by permission of instructor)
Time: Tuesdays, 3-6pm (With the exception of two Thursdays listed below. First meeting: Sept. 18 at Harvard)
Place: Alternating between 16 Divinity Ave., room 1068* and 43 Vassar St., 46-3015;
* Harvard classroom change to new location as of 11/13/07: 16 Divinity Ave., Biolabs room 2080
Requirements: Class participation and term paper

Timetable for term paper:

Specific Aims (1 page) - due 11/27/07
Meetings with Faculty - 11/30/07
Due date for term paper:
MIT students - December 12, 2007
Harvard students - January 11, 2008

Guest lecturers:

• Sydney Brenner (Salk/Janelia Farm)
• Kevin Briggman (MPI-Heidelberg)
• Mitya Chklovskii (Janelia Farm)
• Winfried Denk (MPI-Heidelberg)
• Scott Emmons (Albert Einstein)
• David Hall (Albert Einstein)
• Ken Hayworth (USC)
• Bobby Kasthuri (Harvard)
• Jean Livet (Harvard)
• Carlos Lois (MIT)
• Richard Masland (Harvard)
• Ian Meinertzhagen (Dalhousie)
• Gerry Rubin (Janelia Farm)
• Joshua Sanes (Harvard)
• Stephen Smith (Stanford)
• Peter Sterling (U. Penn.)
• Ian Wickersham (MIT)
• Xiaowei Zhuang (Harvard)

Connectomics is an emerging field defined by the high-throughput generation of data about neural connectivity, and the subsequent mining of that data for knowledge about the brain. A connectome is a summary of the structure of a neural network, an annotated list of all synaptic connections between the neurons inside a brain or brain region. To make connectomics a reality, new tools are needed for the automated generation of three-dimensional nanoscale images of brain tissue, and the automated analysis of the resulting teravoxel or petavoxel datasets. This class will survey tool development in the areas of imaging, cutting, staining, and computation. Nanoscale imaging, including electron microscopy and sub-diffraction-limit fluorescence microscopy. Nanoscale and microscale cutting. Fluorescent and electron-dense staining. Image analysis algorithms. Case studies: C. elegans, fly, neuromuscular innervation, retina, cortex.

• Sept 18 (Harvard)
  • Introduction (Sebastian Seung, Jeff Lichtman, and Sydney Brenner)
  • J. G. White, E. Southgate, J. N. Thomson, and S. Brenner. The structure of the nervous system of the nematode Caenorhabditis elegans. Phil. Trans. Royal Soc. London. B314: 1-340 (1986).
• Sept 27 (MIT)
  • Serial block face imaging (Winfried Denk and Kevin Briggman)
  • W. Denk and H. Horstmann. Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLOS Biol. 2:e329 (2004).
  • K. Briggman and W. Denk. Towards neural circuit reconstruction with volume electron microscopy techniques. Curr. Opin. Neurobiol. 16:562-70 (2006).
• Oct 2 (Harvard)
  • David Hall: "Nervous system reconstruction in C. elegans"
  • Scott Emmons: "Reconstruction of the male nervous system"
  • D. H. Hall and R. L. Russell. The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions. J. Neurosci. 11:1-22 (1991).
  • Z. Altun, Z., R. Lints, and D. H. Hall. Nematode neurons. Anatomy and anatomical methods in Caenorhabditis elegans. Int. Rev. Neurobiol. 69:1-35 (2006).
  • M. M. Barr and L. R. Garcia. Male mating behavior. In wormbook.org (2006).
  • J. E. Sulston, D. G. Albertson, and J. N. Thomson. The Caenorhabditis elegans male: postembryonic development of nongonadal structures. Dev. Biol. 78:542-76 (1980).
• Oct 9 (MIT)
  • Peter Sterling: "What connectomics can explain about the brain"
  • P. Sterling. How retinal circuits optimize the transfer of visual information. In L. M. Chalupa and J. S. Werner, eds. The visual neurosciences. MIT Press. pp. 234-259 (2004).
  • P. Sterling and M. Freed. How robust is a neural circuit? Visual Neuroscience 24: 563-571 (2007).
• Oct 16 (Harvard)
  • Clay Reid: "Function and connectivity in the visual cortex and thalamus"
  • B. G. Cleland. The dorsal lateral geniculate nucleus of the cat. In: Visual Neuroscience, edited by J. D. Pettigrew, K. S. Sanderson, and W. R. Levick. Cambridge Univ. Press, pp. 111-120 (1986).
  • R. C. Reid and W. M. Usrey. Functional Connectivity in the Pathway from Retina to Striate Cortex. In: The Visual Neurosciences, edited by L. M. Chalupa and J. S. Werner. MIT Press, pp. 673-679 (2004).
  • K. Ohki and R. C. Reid. Specificity and randomness in the visual cortex. Current Opinion in Neurobiology 17: 401-407 (2007).
  • Optional additional reading: J. E. Hamos, S. C. Van Horn, D. Raczkowski, and S. M. Sherman. Synaptic Circuits Involving an Individual Retinogeniculate Axon in the Cat. J. Comparative Neurology 259: 165-192 (1987).
• Oct 23 (MIT)
  • Ken Hayworth and Bobby Kasthuri: Nanoscale cutting with ATLUM
  • Ken Hayworth: "High-throughput automation of serial sectioning for the creation of ultrathin section libraries"
  • Richard Masland: "The 'neurome' of a mammalian retina"
  • Reading for Hayworth lecture: Large Scale Analysis of Neural Structures by Ralph C. Merkle. Xerox PARC technical report: CSL-89-10 November 1989, [P89-00173].
  • ATLUM project
  • R. H. Masland. The fundamental plan of the retina. Nature Neuroscience 4: 877-886 (2001).
  • R. H. Masland. Neuronal diversity in the retina. Current Opinion in Neurobiology 11: 431-436 (2001).
  • Optional additional reading for Masland lecture: J.-H. Kong, D. R. Fish, R. L. Rockhill, and R. H. Masland. Diversity of ganglion cells in the mouse retina: unsupervised morphological classification and its limits. J. Comp. Neurology 489: 293-310 (2005).
• Oct 30 (Harvard)
  • Image segmentation and registration (Sebastian Seung)
  • V. Jain, J. F. Murray, F. Roth, S. Turaga, V. Zhigulin, K. L. Briggman, M. N. Helmstaedter, W. Denk, and H. S. Seung. Supervised Learning of Image Restoration with Convolutional Networks. Forthcoming in Proceedings of the IEEE International Conference on Computer Vision (ICCV) 2007, Rio de Janeiro, Brazil (2007, in press).
  • V. Jain, J. F. Murray, F. Roth, S. Turaga, V. Zhigulin, K. L. Briggman, M. N. Helmstaedter, W. Denk, and H. S. Seung. Supervised Learning of Image Restoration with Convolutional Networks - Supplementary Material: Specific Methods.
• Nov 8 (MIT)
  • Ian Meinertzhagen: "Synaptic circuits in the Drosophila visual system: new tools address an old problem"
  • Gerry Rubin: "Molecular Genetic Approaches to Functional Brain Anatomy in Drosophila"
  • I. A. Meinertzhagen and K. E. Sorra. Synaptic organization in the fly's optic lamina: few cells, many synapses and divergent microcircuits. In: Concepts and Challenges in Retinal Biology: A Tribute to John E. Dowling, edited by H. Kolb, H. Ripps and S. Wu. Progress in Brain Research, v. 131: 53-69 (2001).
  • A. Prokop and I. A. Meinertzhagen. Development and structure of synaptic contacts in Drosophila. Seminars in Cell & Developmental Biology 17: 20-30 (2006).
  • Reading for Meinertzhagen lecture: K.-F. Fischbach and A. P. M. Dittrich. The optic lobe of Drosophila melanogaster: I. A Golgi analysis of wild-type structure. Cell and Tissue Research 258: 441-475 (1989).
• Nov 13 (Harvard)
  • Mitya Chklovskii: "From circuit reconstructions to principles of brain design"
  • B. L. Chen, D. H. Hall, and D. B. Chklovskii. Wiring optimization can relate neuronal structure and function. PNAS 103: 4723-4728 (2006).
• Nov 20 (MIT)
  • Jeff Lichtman: "The Principles and Practice of Fluorescence Microscopy"
  • Joshua Sanes: "Expressing Fluorescent Proteins in Neurons"
  • Jean Livet: "Visualizing Neuronal Circuits in Transgenic Mice"
  • J. W. Lichtman and J.-A. Conchello. Fluorescence Microscopy. Nature Methods 2: 910-919 (2005).
  • G. Feng, R. H. Mellor, M. Bernstein, C. Keller-Peck, Q. T. Nguyen, M. Wallace, J. M. Nerbonne, J. W. Lichtman, and J. R. Sanes. Imaging Neuronal Subsets in Transgenic Mice Expressing Multiple Spectral Variants of GFP. Neuron 28: 41-51 (2000).
  • J. Livet, T. A. Weissman, H. Kang, R. W. Draft, J. Lu, R. A. Bennis, J. R. Sanes, and J. W. Lichtman. Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature 450: 56-62 (2007).
• Nov 27 (Harvard - Biolabs room 2080)
  • Jean Livet: "Visualizing Neuronal Circuits in Transgenic Mice" (continuing from Nov. 20th)
  • Ian Wickersham: "Transcomplemented Transsynaptic Tracing"
  • I. R. Wickersham, S. Finke, K.-K. Conzelmann, and E. M. Callaway. Retrograde neuronal tracing with a deletion-mutant rabies virus. Nature Methods 4: 47-49 (2007).
  • I. R. Wickersham, D. C. Lyon, R. J. O. Barnard, T. Mori, S. Finke, K.-K. Conzelmann, J. A. T. Young, and E. M. Callaway. Monosynaptic Restriction of Transsynaptic Tracing from Single, Genetically Targeted Neurons. Neuron 53: 639-647 (2007).
• Dec 4 (MIT)
  • Stephen Smith: "Array Tomography Tools for Neural Circuit Analysis"
  • K. D. Micheva and S. J. Smith. Array Tomography: A New Tool for Imaging the Molecular Architecture and Ultrastructure of Neural Circuits. Neuron 55: 25-36 (2007).
  • S. J. Smith. Circuit Reconstruction Tools Today. Forthcoming in Current Opinion in Neurobiology (2007, in press).
• Dec 11 (Harvard - Biolabs room 2080)
  • Xiaowei Zhuang: "Super-resolution fluorescence imaging"
  • Carlos Lois: "Development and Neuronal Circuit Assembly"
  • W. Kelsch, C. P. Mosley, C.-W. Lin, and C. Lois. Distinct Mammalian Precursors Are Committed to Generate Neurons with Defined Dendritic Projection Patterns. PLoS Biology v. 5, no. 11, e300, doi:10.1371/journal.pbio.0050300 (2007).
  • Readings for Zhuang lecture:
  • S.W. Hell. Far-Field Optical Nanoscopy. Science 316: 1153-1158 (2007).
  • E. Betzig, G. H. Patterson, R. Sougrat, O. W. Lindwasser, S. Olenych, J. S. Bonifacino, M. W. Davidson, J. Lippincott-Schwartz, and H. F. Hess. Imaging Intracellular Fluorescent Proteins at Nanometer Resolution. Science 313: 1642-1645 (2006).
  • M. G. L. Gustafsson. Nonlinear structured-illumination microscopy: Wide-field fluorescence imaging with theoretically unlimited resolution. PNAS 102: 13081-13086 (2005).
  • M. Bates, B. Huang, G. T. Dempsey, and X. Zhuang. Multicolor Super-Resolution Imaging with Photo-Switchable Fluorescent Probes. Science 317: 1749-1753 (2007).
  • M. J. Rust, M. Bates, and X. Zhuang. Sub-diffraction-limit imaging by stochastic optical reconstruction microscopy (STORM). Nature Methods 3: 793-795 (2006).

Most classes are on Tuesday, but there are two exceptions, Thurs Sept. 27 and Thurs Nov. 8, due to conflicts with the Janelia Farm meeting on Neural Circuit Reconstruction and the Society for Neuroscience annual meeting. Like the normal Tuesday classes, the Thursday classes will also be 3-6pm.