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.


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Editorial

Focus on Mapping the Brain

Focus on Mapping the Brain p481

Erika Pastrana

doi:10.1038/nmeth.2509


Focus on Mapping the Brain

Why mapping the brain matters p447

doi:10.1038/nmeth.2513

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


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Historical Perspective

Focus on Mapping the Brain

From the connectome to brain function pp483 - 490

Cornelia I Bargmann & Eve Marder

doi:10.1038/nmeth.2451

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.


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Commentary

Focus on Mapping the Brain

Making sense of brain network data pp491 - 493

Olaf Sporns

doi:10.1038/nmeth.2485

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.


Focus on Mapping the Brain

Why not connectomics? pp494 - 500

Joshua L Morgan & Jeff W Lichtman

doi:10.1038/nmeth.2480

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.


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Perspectives

Focus on Mapping the Brain

Cellular-resolution connectomics: challenges of dense neural circuit reconstruction pp501 - 507

Moritz Helmstaedter

doi:10.1038/nmeth.2476

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.


Focus on Mapping the Brain

CLARITY for mapping the nervous system pp508 - 513

Kwanghun Chung & Karl Deisseroth

doi:10.1038/nmeth.2481

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.


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Reviews

Focus on Mapping the Brain

Mapping brain circuitry with a light microscope pp515 - 523

Pavel Osten & Troy W Margrie

doi:10.1038/nmeth.2477

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.


Focus on Mapping the Brain

Imaging human connectomes at the macroscale pp524 - 539

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

doi:10.1038/nmeth.2482

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.


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Resource

Focus on Mapping the Brain

Improved tools for the Brainbow toolbox pp540 - 547

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

doi:10.1038/nmeth.2450

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.


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