Volume 10 Issue 6, June 2013

Volume 10 Issue 6

Visualization of functional connectivity in the human cerebral cortex based on magnetic resonance imaging data. Brain image by Joachim Böttger and Daniel Margulies (Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany) with compositing by Tobias S. Hoffmann. Cover composition by Erin Dewalt. Focus p479

Editorials

  • Editorial |

    Obtaining anatomical maps and molecular information of brain circuits and their activity patterns in relation to specific behaviors is instrumental to understanding brain function.

This Month

  • This Month |

    New features are added to a neuron-painting toolbox that could contribute to the recently announced US brain-mapping initiative.

    • Vivien Marx
  • This Month |

    Choose distinct symbols that overlap without ambiguity and communicate relationships in data.

    • Martin Krzywinski
    •  & Bang Wong

Correspondence

Research Highlights

Technology Feature

News and Views

  • News & Views |

    Two reports describing the use of direct-conversion electron detectors and algorithms that correct for beam-induced sample motion in single-particle electron cryomicroscopy demonstrate that this technique can solve structures of macromolecules at near-atomic resolution.

    • Robert M. Glaeser

Historical Perspective

  • Historical Perspective |

    In this Historical Perspective, we ask what information is needed beyond connectivity diagrams to understand the function of nervous systems. Informed by invertebrate circuits whose connectivities are known, we highlight the importance of neuronal dynamics and neuromodulation, and the existence of parallel circuits. The vertebrate retina has these features in common with invertebrate circuits, suggesting that they are general across animals. Comparisons across these systems suggest approaches to study the functional organization of large circuits based on existing knowledge of small circuits.

    • Cornelia I Bargmann
    •  & Eve Marder

Commentaries

  • Commentary |

    New methods for mapping synaptic connections and recording neural signals generate rich and complex data on the structure and dynamics of brain networks. Making sense of these data will require a concerted effort directed at data analysis and reduction as well as computational modeling.

    • Olaf Sporns
  • Commentary |

    Opinions diverge on whether mapping the synaptic connectivity of the brain is a good idea. Here we argue that albeit their limitations, such maps will reveal essential characteristics of neural circuits that would otherwise be inaccessible.

    • Joshua L Morgan
    •  & Jeff W Lichtman

Perspectives

  • Perspective |

    Neuronal networks are high-dimensional graphs that are packed into three-dimensional nervous tissue at extremely high density. Comprehensively mapping these networks is therefore a major challenge. Although recent developments in volume electron microscopy imaging have made data acquisition feasible for circuits comprising a few hundreds to a few thousands of neurons, data analysis is massively lagging behind. The aim of this Perspective is to summarize and quantify the challenges for data analysis in cellular-resolution connectomics and describe current solutions involving online crowd-sourcing and machine-learning approaches.

    • Moritz Helmstaedter
  • Perspective |

    With potential relevance for brain-mapping work, hydrogel-based structures can now be built from within biological tissue to allow subsequent removal of lipids without mechanical disassembly of the tissue. This process creates a tissue-hydrogel hybrid that is physically stable, that preserves fine structure, proteins and nucleic acids, and that is permeable to both visible-spectrum photons and exogenous macromolecules. Here we highlight relevant challenges and opportunities of this approach, especially with regard to integration with complementary methodologies for brain-mapping studies.

    • Kwanghun Chung
    •  & Karl Deisseroth

Reviews

  • Review Article |

    The beginning of the 21st century has seen a renaissance in light microscopy and anatomical tract tracing that together are rapidly advancing our understanding of the form and function of neuronal circuits. The introduction of instruments for automated imaging of whole mouse brains, new cell type–specific and trans-synaptic tracers, and computational methods for handling the whole-brain data sets has opened the door to neuroanatomical studies at an unprecedented scale. We present an overview of the present state and future opportunities in charting long-range and local connectivity in the entire mouse brain and in linking brain circuits to function.

    • Pavel Osten
    •  & Troy W Margrie
  • Review Article |

    At macroscopic scales, the human connectome comprises anatomically distinct brain areas, the structural pathways connecting them and their functional interactions. Annotation of phenotypic associations with variation in the connectome and cataloging of neurophenotypes promise to transform our understanding of the human brain. In this Review, we provide a survey of magnetic resonance imaging–based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry and emphasize the importance of integrating structural and functional perspectives on brain architecture.

    • R Cameron Craddock
    • , Saad Jbabdi
    • , Chao-Gan Yan
    • , Joshua T Vogelstein
    • , F Xavier Castellanos
    • , Adriana Di Martino
    • , Clare Kelly
    • , Keith Heberlein
    • , Stan Colcombe
    •  & Michael P Milham

Resource

  • Resource |

    An improved Brainbow toolbox for expression in the mouse is presented in this Resource. The collection includes transgenic lines, plasmids and viral vectors with improved performance and added capabilities relative to the original Brainbow constructs.

    • Dawen Cai
    • , Kimberly B Cohen
    • , Tuanlian Luo
    • , Jeff W Lichtman
    •  & Joshua R Sanes

Brief Communications

  • Brief Communication |

    Contact spotting with standard microarray printing tools can be used to generate high-density arrays of living mammalian cells, permitting the arraying of cell libraries without complex fluid manipulation.

    • Kristina Woodruff
    • , Luis M Fidalgo
    • , Samy Gobaa
    • , Matthias P Lutolf
    •  & Sebastian J Maerkl

Articles

  • Article |

    A method for computing the intrinsic resolution of a super-resolution image that accounts for localization uncertainty, labeling density and image anisotropy is described. This work extends and builds on the Fourier ring correlation method used in cryoelectron microscopy.

    • Robert P J Nieuwenhuizen
    • , Keith A Lidke
    • , Mark Bates
    • , Daniela Leyton Puig
    • , David Grünwald
    • , Sjoerd Stallinga
    •  & Bernd Rieger
  • Article |

    Unlike hybrid approaches that use multiple libraries for de novo assembly, the hierarchical genome-assembly process uses data from only a single long-read SMRT sequencing library to produce high-quality finished microbial genome or BAC assemblies in an automated workflow.

    • Chen-Shan Chin
    • , David H Alexander
    • , Patrick Marks
    • , Aaron A Klammer
    • , James Drake
    • , Cheryl Heiner
    • , Alicia Clum
    • , Alex Copeland
    • , John Huddleston
    • , Evan E Eichler
    • , Stephen W Turner
    •  & Jonas Korlach
  • Article |

    With a multiplexed, sensitive, selected reaction monitoring–based mass spectrometry approach, transcription factor copy numbers can be accurately quantified during terminal fat cell differentiation.

    • Jovan Simicevic
    • , Adrien W Schmid
    • , Paola A Gilardoni
    • , Benjamin Zoller
    • , Sunil K Raghav
    • , Irina Krier
    • , Carine Gubelmann
    • , Frédérique Lisacek
    • , Felix Naef
    • , Marc Moniatte
    •  & Bart Deplancke
  • Article |

    A method to measure reversals in gene expression between cell types is used to identify transcriptional regulators important for lineage specification. The approach should help identify putative factors for direct fate conversion.

    • Merja Heinäniemi
    • , Matti Nykter
    • , Roger Kramer
    • , Anke Wienecke-Baldacchino
    • , Lasse Sinkkonen
    • , Joseph Xu Zhou
    • , Richard Kreisberg
    • , Stuart A Kauffman
    • , Sui Huang
    •  & Ilya Shmulevich
  • Article |

    The combination of a direct electron-detection camera that can count individual electrons and an algorithm for correcting for beam-induced motion in cryo-EM will facilitate determination of three-dimensional structures of smaller, lower-symmetry macromolecular complexes to higher resolution than previously possible.

    • Xueming Li
    • , Paul Mooney
    • , Shawn Zheng
    • , Christopher R Booth
    • , Michael B Braunfeld
    • , Sander Gubbens
    • , David A Agard
    •  & Yifan Cheng

Application Note

Focus

  • Focus |

    Focus on Mapping the Brain

    We are entering a new era in the neurosciences, in which development of technology will be in the spotlight. In this Focus, experts outline the different technologies needed to obtain anatomical and functional brain maps across species, and discuss the importance of assembling these maps and what will be needed beyond them, to understand the functioning of the brain.