Skip to main content
Article thumbnail
Location of Repository

A Computational Framework for Ultrastructural Mapping of Neural Circuitry

By James R Anderson, Bryan W Jones, Jia-Hui Yang, Marguerite V Shaw, Carl B Watt, Pavel Koshevoy, Joel Spaltenstein, Elizabeth Jurrus, Kannan UV, Ross T Whitaker, David Mastronarde, Tolga Tasdizen and Robert E Marc

Abstract

Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components) are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM) remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM) image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM), mosaicking and registration (ir-tools), and large slice viewers (MosaicBuilder, Viking) can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina), terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally, this framework provides a mechanism for parallelization of ssTEM imaging, volume assembly, and data analysis across an international user base, enhancing the productivity of a large cohort of electron microscopists

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:2661966
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (1985). (3H) glycine-accumulating neurons of the human retina.
    2. (2002). A molecular phenotype atlas of the zebrafish retina.
    3. (1998). A Novel signaling pathway from rod photoreceptors to ganglion cells in mammalian retina.
    4. (1980). A systematic approach to reconstructing microcircuitry by electron microscopy of serial sections.
    5. (2008). A technicolour approach to the connectome.
    6. (1996). Absence of spectrally specific lateral inputs to midget ganglion cells in primate retina.
    7. (1996). Amino acid signatures in the primate retina.
    8. (1986). An ultrastructural study of interplexiform cell synapses in the human retina.
    9. (2003). Anatomical substrates for functional columns in macaque monkey primary visual cortex.
    10. (2007). Array tomography: a new tool for imaging the molecular architecture and ultrastructure of neural circuits.
    11. (2005). Automated electron microscope tomography using robust prediction of specimen movements.
    12. (2006). Automating the collection of ultrathin serial sections for large volume TEM reconstructions.
    13. (2008). Axon tracking in serial block-face scanning electron microscopy.
    14. (2008). Behavioral phenotyping strategies for mutant mice.
    15. (1996). Cellular biophysics: electrical properties.
    16. (2001). Cellular diversity in mouse neocortex revealed by multispectral analysis of amino acid immunoreactivity.
    17. (2002). Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina.
    18. (2008). Contourpropagation algorithms for semi-automated reconstruction of neural processes.
    19. (2004). Cortical rewiring and information storage.
    20. (2002). Coupling pattern of S1 and S2 amacrine cells in the rabbit retina.
    21. (2003). Dopaminergic amacrine cells in the inner nuclear layer and ganglion cell layer comprise a single functional retinal mosaic.
    22. (2000). Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations.
    23. (1983). Electroanatomy of a unique amacrine cell in the rabbit retina.
    24. (1995). Electron microscopy and three-dimensional image reconstruction.
    25. (2001). Extending unbiased stereology of brain ultrastructure to three-dimensional volumes.
    26. (2008). Extreme retinal remodeling triggered by light damage: implications for age related macular degeneration.
    27. (2000). Fundamental GABAergic amacrine cell circuitries in the retina: nested feedback, concatenated inhibition, and axosomatic synapses.
    28. (2000). Glutamate, GABA and precursor amino acids in adult mouse neocortex: cellular diversity revealed by quantitative immunocytochemistry.
    29. (2004). How retinal circuits optimize the transfer of visual information.Chalupa
    30. (1999). Kainate activation of horizontal, bipolar, amacrine, and ganglion cells in the rabbit retina.
    31. (2007). Light and electron microscopic localization of multiple proteins using quantum dots.
    32. (2003). Macaque retina contains an S-cone OFF midget pathway.
    33. (1999). Mapping glutamatergic drive in the vertebrate retina with a channel-permeant organic cation.
    34. (2007). Microcircuitry for two types of achromatic ganglion cell in primate fovea.
    35. (2001). Microcircuits for night vision in mouse retina.
    36. (2002). Molecular phenotyping of retinal ganglion cells.
    37. (1986). Molecular specificity of defined types of amacrine synapse in cat retina.
    38. (1986). Morphological identification of serotonin-accumulating neurons in the living retina.
    39. (2008). Mosaics, tiling and coverage by retinal neurons. The senses: a comprehensive reference vision.Masland
    40. (2003). Neural remodeling in retinal degeneration.
    41. (2007). Neural reprogramming in retinal degeneration.
    42. (2001). Neuronal diversity in the retina.
    43. (1993). OFF-alpha and OFF-beta ganglion cells in cat retina: II. Neural circuitry as revealed by electron microscopy of HRP stains.
    44. (1995). Pattern recognition of amino acid signatures in retinal neurons.
    45. (1990). Patterns of glutamate immunoreactivity in the goldfish retina.
    46. (1988). Pharmacological modulation of the rod pathway in the cat retina.
    47. (2005). Reconstruct: a free editor for serial section microscopy.
    48. (2008). Retinal ganglion cell types and their central projections.Masland RH, Albright T, editors. The senses: a comprehensive reference vision.
    49. (2003). Retinal remodeling triggered by photoreceptor degenerations.
    50. (1974). Rod and cone pathways in the retina of the cat.
    51. (2004). Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure.
    52. (2008). Serial section scanning electron microscopy of adult brain tissue using focused ion beam milling.
    53. (1992). Synaptic connections of the narrow-field, bistratified rod amacrine cell (AII) in the rabbit retina.
    54. (2006). Systematic analysis of the visual projection neurons of Drosophila melanogaster - I: lobula-specific pathways.
    55. (2002). The diversity of ganglion cells in a mammalian retina.
    56. (2005). The human connectome: a structural description of the human brain.
    57. (1997). The organization of pyramidal cells in area 18 of the rhesus monkey.
    58. (2004). The population of bipolar cells in the rabbit retina.
    59. (1991). The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions.
    60. (1989). The role of glycine in the mammalian retina.Osborne
    61. (1999). The shapes and numbers of amacrine cells: matching of photofilled with Golgistained cells in the rabbit retina and comparison with other mammalian species.
    62. (1976). The structure of the ventral nerve cord of Caenorhabditis elegans.
    63. (1995). The theoretical foundation of dendritic function: selected papers of Wilfred Rall with commentaries.Segev I,
    64. (1972). Three-dimensional reconstruction from serial sections.
    65. (1997). Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation.
    66. (2002). Three-dimensional structure of synapses in the brain and on the web. In:
    67. (1980). Toward a functional architecture of the retina: serial reconstruction of adjacent ganglion cells.
    68. (2006). Towards neural circuit reconstruction with volume electron microscopy techniques.
    69. (2006). Uniform serial sectioning for transmission electron microscopy.
    70. (2006). Wiring optimization can relate neuronal structure and function.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.