Neuroscience articles within Nature Methods

Featured

  • 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
    •  & Michael P Milham

  • 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

  • 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

  • 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
    •  & Joshua R Sanes

  • Research Highlights |

    A digital atlas of enhancers active in the developing mammalian brain is available for exploration.

    • Erika Pastrana

  • Research Highlights |

    An electrochemical gene-delivery method enables rapid modification of gene expression in postmitotic neurons in vivo, changing their identity and connectivity pattern.

    • Erika Pastrana

  • This Month |

    Engineering protein sensors to light up split-second signals in the brain

    • Vivien Marx

  • Article |

    A single-wavelength genetically encoded sensor of extracellular glutamate is reported. The sensor—iGluSnFR—is bright and photostable under both one- and two-photon illumination and is shown to work for in vivo imaging in worms, zebrafish and mice.

    • Jonathan S Marvin
    • , Bart G Borghuis
    •  & Loren L Looger

  • Brief Communication |

    Using the red shifted opsin C1V1T and simple raster-scanning illumination, this work shows two-photon optogenetic stimulation of single cells, dendrites and spines. The method is also applied to map synaptic circuits in mouse brain slices and, using holographic photostimulation, for the simultaneous activation of two neurons located in different planes. Also online, Prakash et al. present a collection of opsins for two-photon excitation, inhibition and bistable control of neuronal activity in vitro and in vivo.

    • Adam M Packer
    • , Darcy S Peterka
    •  & Rafael Yuste

  • Resource |

    A collection of opsins for two-photon modulation of neuronal activity in vitro and in vivo is presented in this resource. The opsins have kinetic, expression and spectral properties ideally suited to typical raster-scanning two-photon microscopy. Also online, Packer et al. use the red-shifted opsin C1V1T and simple raster-scanning illumination to stimulate individual spines and dendrites and map synaptic circuits.

    • Rohit Prakash
    • , Ofer Yizhar
    •  & Karl Deisseroth

  • Research Highlights |

    A freely accessible transcriptional atlas offers unprecedented possibilities for exploring the human brain.

    • Erika Pastrana

  • Brief Communication |

    A method for staining and embedding the entire mouse brain for electron microscopy is reported. The method results in uniform myelin staining and will allow reconstructions of myelinated long-range axons using serial block-face electron microscopy.

    • Shawn Mikula
    • , Jonas Binding
    •  & Winfried Denk

  • Article |

    Development of the bright green and red fluorescent proteins, Clover and mRuby2, creates a fluorescence resonance energy transfer (FRET) pair with the highest Förster radius among existing ratiometric FRET pairs. Substitution of this pair for current FRET pairs in several existing sensors reliably and substantially improves sensor performance.

    • Amy J Lam
    • , François St-Pierre
    •  & Michael Z Lin

  • News & Views |

    Through a collaborative effort, engineers and neuroscientists have created a method, using electrospun nanofibers as surrogate neuronal axons, to piece together the complexities of myelination.

    • Ragnhildur Thóra Káradóttir
    •  & John Henry Stockley

  • Brief Communication |

    An integrated system composed of a microfluidic device, computer-vision tools and statistical methods for automatically handling, imaging, classifying and sorting C. elegans organisms is presented. The system performs automated screens of subcellular phenotypes and is used here to identify genes involved in synaptogenesis.

    • Matthew M Crane
    • , Jeffrey N Stirman
    •  & Hang Lu

  • Research Highlights |

    Codifferentiating human pluripotent stem cells along neural and endothelial lineages provides cues to efficiently generate blood-brain barrier endothelial cells.

    • Natalie de Souza

  • Article |

    An imaging and registration framework called Virtual Brain Explorer for Zebrafish (ViBE-Z) allows mapping of gene expression patterns and anatomical structures in the zebrafish larval brain. ViBE-Z is provided via a web interface and contains software for image processing, data sets from several developmental stages and a brain atlas.

    • Olaf Ronneberger
    • , Kun Liu
    •  & Wolfgang Driever

  • Article |

    Simultaneous multiview light-sheet microscopy using two illumination and two detection arms with one- or two-photon illumination is coupled to a fast data acquisition framework and analysis pipeline for quantitative imaging and tracking of individual cells and the developing nervous system throughout a living fly embryo. A related paper by Krzic et al. is also in this issue.

    • Raju Tomer
    • , Khaled Khairy
    •  & Philipp J Keller

  • Research Highlights |

    Fly rhythms under natural light and temperature differ from those in the lab.

    • Monya Baker

  • News & Views |

    Fluorescence recording of neural activity in the magnetic resonance scanner is a new strategy for examining the cellular underpinnings of blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI).

    • Serge Charpak
    •  & Bojana Stefanovic

  • Brief Communication |

    A robot, algorithm and software for automated in vivo intracellular electrophysiology are reported that can automatically perform whole-cell patch clamping in the living mouse brain with quality comparable to that for a trained human experimenter.

    • Suhasa B Kodandaramaiah
    • , Giovanni Talei Franzesi
    •  & Craig R Forest

  • Article |

    Simultaneous functional magnetic resonance imaging (fMRI) and fiber-optic–based calcium recordings in rats allow investigation of the relationship between blood oxygen level–dependent (BOLD) fMRI signals and the underlying neural activity. The study uncovers prolonged BOLD signal components involving glial activation.

    • Kristina Schulz
    • , Esther Sydekum
    •  & Fritjof Helmchen

  • Research Highlights |

    Downregulation of natural antisense transcripts enhances expression of their sense counterparts.

    • Nicole Rusk

  • Research Highlights |

    Two methodological approaches allow researchers to manipulate the formation and reactivation of memories in mice.

    • Erika Pastrana

  • Brief Communication |

    To increase the efficiency of direct neuronal conversion of postnatal human fibroblasts, the authors combine two-factor neuronal programming with small molecules. This method increases the yield and purity of functional neuron-like cells by more than 15-fold.

    • Julia Ladewig
    • , Jerome Mertens
    •  & Oliver Brüstle

  • Article |

    We describe software, MiceProfiler, for automatic tracking of two interacting mice and analysis of their social interactions without the need of animal tagging. The program allows the identification of key elements that trigger social contact in different mouse strains.

    • Fabrice de Chaumont
    • , Renata Dos-Santos Coura
    •  & Jean-Christophe Olivo-Marin

  • Article |

    A photoisomerizable molecule, quaternary ammonium–azobenzene–quaternary ammonium (QAQ) enables reversible optical silencing of nociceptive neurons. The selective entry of QAQ into active nociceptive neurons allows spatially and temporally precise regulation of nociceptor activity in vitro and in vivo.

    • Alexandre Mourot
    • , Timm Fehrentz
    •  & Richard H Kramer

  • News & Views |

    In vivo methods to capture processing events such as RNA editing in specific cell types are sparse. Researchers have now developed a method to visualize adenosine-to-inosine editing activity in individual fruit fly neurons using a reverse-engineered fluorescent reporter.

    • Chammiran Daniel
    •  & Marie Öhman

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