9.691/MCB 206 Introduction to Connectomics

http://hebb.mit.edu/courses/connectomics/
Joint Harvard-MIT graduate seminar class, Fall 2009
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, 3:30-6:30pm (With the exception of one Thursday listed below. First meeting: Sept. 15)
Place: All classes will be held at Harvard, 52 Oxford St. (Northwest Building), Room 425
Requirements: Class participation and term paper

You can also access the 2007 web page for this class.

Term paper

Specific Aims (1 page): Nov. 16
Meetings with Faculty: Nov. 17
Revised Specific Aims: Nov. 24
Full Paper: Dec. 10

Guest lecturers

• Helen Barbas (BU)
• Daniel Berger (MIT)
• Davi Bock (Harvard)
• Kevin Briggman (MPI-Heidelberg)
• Mitya Chklovskii (Janelia Farm)
• Scott Emmons (Albert Einstein)
• David Hall (Albert Einstein)
• Ken Hayworth (Harvard)
• Moritz Helmstaedter (MPI-Heidelberg)
• Viren Jain (MIT)
• Bobby Kasthuri (Harvard)
• Richard Masland (Harvard)
• Partha Mitra (Cold Spring Harbor Labs)
• Kathy Rockland (MIT)
• Joshua Sanes (Harvard)
• Clif Saper (Harvard)
• Stephen Smith (Stanford)
• Srini Turaga (MIT)
• Ian Wickersham (MIT)
• and others TBA

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. 15
  • 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).
  • D. H. Hall, R. Lints, and Z. Altun. 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).
• Sept. 29
  • Ken Hayworth and Bobby Kasthuri: Automating Large Volume Reconstruction at the Nanometer Scale by Creating Ultra-thin Slice Libraries
  • Daniel Berger: TBA
  • Ralph C. Merkle. Large Scale Analysis of Neural Structures. Xerox PARC technical report: CSL-89-10 November 1989, [P89-00173].
  • ATLUM project
• Oct. 6
  • Clay Reid: Function and connectivity in the visual cortex and thalamus
  • Davi Bock: Fast imaging systems for large-scale EM reconstructions of neural circuits
  • 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).
  • 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).
  • Optional additional reading:
  • K. Ohki and R. C. Reid. Specificity and randomness in the visual cortex. Current Opinion in Neurobiology 17: 401-407 (2007).
  • 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).
• Oct. 13
  • Richard Masland: The "neurome" of a mammalian retina
  • Josh Sanes: The retinome: molecular genetics to the rescue
  • 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).
  • I.-J. Kim, Y. Zhang, M. Yamagata, M. Meister, and J. R. Sanes. Molecular identification of a retinal cell type that responds to upward motion. Nature 452: 478-82 (2008).
  • S. Siegert, B. G. Scherf, K. Del Punta, N. Didkovsky, N. Heintz, B. Roska. Genetic address book for retinal cell types. Nat Neurosci. 12: 1197-1204 (2009).
• Oct. 22
  • Kevin Briggman: Serial block face imaging
  • Moritz Helmstaedter: Reconstruction of neural circuits from Serial Blockface EM data: manual tracing, automation, reliability
  • 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).
  • M. Helmstaedter, K. L. Briggman, and W. Denk. 3D structural imaging of the brain with photons and electrons. Curr. Opin. Neurobiol. 18:633-41 (2008).
• Oct. 27
  • Ian Wickersham: Transcomplemented Transsynaptic Tracing
  • Kathy Rockland: Facts and myths about the cortical column
  • 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).
  • K. Rockland and N. Ichinohe. Some thoughts on cortical minicolumns. Exp. Brain Res. 158:265-277 (2004).
  • H. Markram. Fixing the location and dimensions of a functional neocortical column. HFSP Journal 2:132-5 (2008).
  • J. C. Horton and D. L. Adams. The cortical column: a structure without a function. Phil. Trans. R. Soc. B2005:837-862 (2005)
• Nov. 3
  • Stephen Smith: Array Tomography Tools for Neural Circuit Analysis
  • Partha Mitra. Brain Architecture: Studying Neural Circuitry at a Brain Wide Scale
  • 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. Current Opinion in Neurobiology 17:601-8 (2007).
  • J. W. Bohland et al. A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale. PLoS Comput. Biol. 5:e1000334 (2009).
• Nov. 10
  • Viren Jain: TBA
  • Srini Turaga: TBA
  • Sebastian Seung: Latent variable models for connectomes
  • 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. Proceedings of the IEEE International Conference on Computer Vision (ICCV) 2007, Rio de Janeiro, Brazil (2007).
  • 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.
  • H. S. Seung. Reading the book of memory: sparse sampling versus dense mapping of connectomes. Neuron 62:17-29 (2009).
• Nov. 17
  • 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. 24
  • Clif Saper: Use of genetically driven tracers to identify chemically defined circuitry in the CNS
  • Helen Barbas: Prefrontal pathways for excitatory and inhibitory control: from systems to synapses.
  • Sakurai T, Nagata R, Yamanaka A, Kawamura H, Tsujino N, Muraki Y, Kageyama H, Kunita S, Takahashi S, Goto K, Koyama Y, Shioda S, Yanagisawa M. Input of orexin/hypocretin neurons revealed by a genetically encoded tracer in mice. Neuron. 46:297-308 (2005).
  • DeFalco J, Tomishima M, Liu H, Zhao C, Cai X, Marth JD, Enquist L, Friedman JM. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science. 291:2608-13 (2001).
  • Horowitz LF, Montmayeur JP, Echelard Y, Buck LB. A genetic approach to trace neural circuits. Proc Natl Acad Sci USA. 96:3194-9 (1999).
  • Chamberlin NL, Du B, de Lacalle S, Saper CB. Recombinant adeno-associated virus vector: use for transgene expression and anterograde tract tracing in the CNS. Brain Res. 793:169-75 (1998)
  • B. Zikopoulos and H. Barbas. Parallel Driving and Modulatory Pathways Link the Prefrontal Cortex and Thalamus. PLoS ONE 2:e848 (2007).
  • M. Medalla and H. Barbas. Synapses with Inhibitory Neurons Differentiate Anterior Cingulate from Dorsolateral Prefrontal Pathways Associated with Cognitive Control. Neuron 61:609-620 (2009)
• Dec. 1
  • Jeff Lichtman: Connectomics in the Developing Nervous System
  • 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).
  • Ju Lu, Juan Carlos Tapia, Olivia L. White, Jeff W. Lichtman. The Interscutularis Muscle Connectome PLoS Biol 7 doi:10.1371/journal.pbio.1000032

Most classes are on Tuesday, but there is one exception, Thurs Oct. 22, due to conflict with the Society for Neuroscience annual meeting. Also there is no class the week of Sept. 21, due to the HHMI-MPG meeting on Neural Circuit Reconstruction. Like the normal Tuesday classes, the Thursday class will also be 3:30-6:30pm.