Featured
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Brief Communication |
An artery-specific fluorescent dye for studying neurovascular coupling
The authors report Alexa Fluor 633 hydrazide to be artery-specific and use it to measure arteriole dilation dynamics in vivo in response to visual stimuli in mouse, rat and cat neocortex. They find that sensory stimulus–evoked arteriole dilation reduces the fluorescence recorded from underlying neurons.
- Zhiming Shen
- , Zhongyang Lu
- & Prakash Kara
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Article |
Controlling airborne cues to study small animal navigation
A device for generating precise spatial and temporal patterns of airborne odorants is reported. In combination with machine vision tracking software, the authors use the device to monitor navigation of freely moving Drosophila melanogaster larvae.
- Marc Gershow
- , Matthew Berck
- & Aravinthan D T Samuel
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Article |
Fast two-photon in vivo imaging with three-dimensional random-access scanning in large tissue volumes
An acousto-optic two-photon microscope with continuous three-dimensional trajectory and random-access scanning modes can scan near-cubic-millimeter volumes of tissue at sub-millisecond temporal resolution in vivo. The system can be used to image both sub-cellular as well as network-scale neuronal activity.
- Gergely Katona
- , Gergely Szalay
- & Balázs Rózsa
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Article |
Visualizing adenosine-to-inosine RNA editing in the Drosophila nervous system
Adenosine-to-inosine RNA editing modifies expressed sequences and enhances functional protein diversity. The authors report an in vivo fluorescent reporter that provides a readout of adenosine deaminase RNA-editing activity in Drosophila melanogaster neurons, showing evidence of inter-individual variability in editing activity.
- James E C Jepson
- , Yiannis A Savva
- & Robert A Reenan
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Analysis |
Principles for applying optogenetic tools derived from direct comparative analysis of microbial opsins
In this Analysis, the authors directly experimentally compare microbial opsins used for the control of neural activity. They extract essential principles and key parameters that can help end users with the design and interpretation of optogenetic experiments and guide tool developers in the characterization of future tools.
- Joanna Mattis
- , Kay M Tye
- & Karl Deisseroth
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Article |
mGRASP enables mapping mammalian synaptic connectivity with light microscopy
In this paper, the authors report GFP reconstitution across synaptic partners (GRASP) adapted for synapse visualization in the mammalian brain.
- Jinhyun Kim
- , Ting Zhao
- & Jeffrey C Magee
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News & Views |
The Lego-logic of optogenetics
Daisy-chaining light-sensitive ion channels, pumps and fluorescent proteins extends the possibilities for control of neuronal activity.
- Thomas G Oertner
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Article |
Optical recording of action potentials in mammalian neurons using a microbial rhodopsin
The microbial rhodopsin protein, Archaerhodopsin 3, can function as a rapid and highly sensitive genetically encoded voltage indicator in mammalian cells that is capable of detecting single action potentials with a signal-to-noise ratio greater than 10. A mutant lacking proton pumping displays greater sensitivity but a slowed response.
- Joel M Kralj
- , Adam D Douglass
- & Adam E Cohen
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Brief Communication |
Embryonic stem cell–based mapping of developmental transcriptional programs
Presented is a study of gene regulation during development using a combination of chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq) and directed differentiation of mouse embryonic stem cells inducibly expressing epitope-tagged transcription factors.
- Esteban O Mazzoni
- , Shaun Mahony
- & Hynek Wichterle
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Article |
A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins
Molecular engineering allows stoichiometric and co-localized expression of two optogenetic actuators, spaced by a fluorescent protein and an additional transmembrane helix in a single protein fusion. The method provides modular optogenetic tools for bidirectional membrane potential control or synergistic effects on neuronal activity.
- Sonja Kleinlogel
- , Ulrich Terpitz
- & Ernst Bamberg
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Research Highlights |
Molecular matchmaking for neural control
Engineered ion channels and cognate synthetic ligands expand the catalog of tools to study brain function.
- Petya V Krasteva
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This Month |
Paul Tesar
Pure oligodendrocyte populations can be made without cell sorting.
- Monya Baker
- & Paul Tesar
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Brief Communication |
Population-specific expression analysis (PSEA) reveals molecular changes in diseased brain
A computational approach for analysis of gene expression in heterogeneous samples of varying composition is presented. The authors used it to study expression in brain samples from humans with Huntington's disease.
- Alexandre Kuhn
- , Doris Thu
- & Ruth Luthi-Carter
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Article |
Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells
Reported is the robust directed differentiation of mouse epiblast stem cells to oligodendrocyte precursor cells, which then differentiate into myelinating oligodendrocytes in vitro and in vivo. The system should prove useful for basic research and for drug screens.
- Fadi J Najm
- , Anita Zaremba
- & Paul J Tesar
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Research Highlights |
Watching neurotransmission in vitro
An in vitro system for neurotransmitter release is reported.
- Natalie de Souza
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News in Brief |
Optogenetic tools for social disorders
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Resource |
Cell type–specific channelrhodopsin-2 transgenic mice for optogenetic dissection of neural circuitry function
A collection of functionally characterized BAC transgenic mouse lines in which the channelrhodopsin-2 H134R variant is specifically and stably expressed in GABAergic, cholinergic, serotonergic or parvalbumin-positive neurons is reported.
- Shengli Zhao
- , Jonathan T Ting
- & Guoping Feng
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Research Highlights |
Thwarting amyloid fibers
Two structure-driven studies of the culprits behind diseases associated with amyloid fibers give clues to stopping these agents in their tracks.
- Irene Kaganman
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Article |
Large-scale automated synthesis of human functional neuroimaging data
A framework and web interface for the large-scale and automated synthesis of human neuroimaging data extracted from the literature is presented. It is used to generate a large database of mappings between neural and cognitive states and to address long-standing inferential problems in the neuroimaging literature.
- Tal Yarkoni
- , Russell A Poldrack
- & Tor D Wager
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Article |
High-content behavioral analysis of Caenorhabditis elegans in precise spatiotemporal chemical environments
Quantitative analysis of Caenorhabditis elegans chemosensory behavior is achieved in a structured arena with microfluidic delivery of stimuli with precise spatial and temporal control. Also in this issue, Swierczek et al. report software for real-time behavioral analysis in worms.
- Dirk R Albrecht
- & Cornelia I Bargmann
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Brief Communication |
Near-infrared branding efficiently correlates light and electron microscopy
Fiducial marks that can be visualized by both light and electron microscopy are generated by 'branding' fixed tissue with a near-infrared laser and will facilitate correlative light and electron microscopy.
- Derron Bishop
- , Ivana Nikić
- & Thomas Misgeld
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Article |
High-throughput behavioral analysis in C. elegans
The Multi-Worm Tracker permits real-time, high-throughput, quantitative analysis of behavior in Caenorhabditis elegans. It should enable screens for genes implicated in complex worm behaviors. Also in this issue, Albrecht and Bargmann apply microfluidics to study worm chemosensory behavior with high spatial and temporal precision.
- Nicholas A Swierczek
- , Andrew C Giles
- & Rex A Kerr
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Research Highlights |
Perfecting ChR2
Two new reports describe variants of channelrhodopsin 2 with improved properties.
- Erika Pastrana
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Article |
BrainAligner: 3D registration atlases of Drosophila brains
Software for the automated and accurate registration of multiple images of Drosophila melanogaster brain is reported. It is used to build a preliminary atlas of gene expression in the fly brain.
- Hanchuan Peng
- , Phuong Chung
- & Julie H Simpson
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Research Highlights |
News in brief
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Research Highlights |
Brain function marries anatomy
Researchers have taken first steps toward functional connectomics. By combining large-scale serial electron microscopy and functional imaging data, the structure of neural networks can be related to their function.
- Erika Pastrana
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Research Highlights |
News in brief
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Research Highlights |
Building a megabrain atlas
A digital platform has been created to incorporate multiple brain data resources into a common global mouse atlas.
- Erika Pastrana
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Article |
Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph
A miniature portable tomograph allows the imaging of awake, behaving rats with positron emission tomography while simultaneously measuring their behavior. This method for noninvasive whole-brain imaging can link studies of brain activity with particular behaviors.
- Daniela Schulz
- , Sudeepti Southekal
- & Paul Vaska
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Research Highlights |
Brains gone wild
Analyzing brain signals from freely moving rodents in the wild is possible using a wireless neural recording system.
- Erika Pastrana
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Article |
A microprobe for parallel optical and electrical recordings from single neurons in vivo
A dual-core microprobe for in vivo optical and electrical recordings in deep layers of the central nervous system at single-cell resolution.
- Yoan LeChasseur
- , Suzie Dufour
- & Yves De Koninck
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Article |
Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster
A genetic multicolor cell-labeling technique for Droshophila melanogaster, Flybow, is described and applied to the study of neural circuits. This method implements a variant of the mouse Brainbow strategy in combination with specific neuronal targeting using the Gal-4–upstream activating sequence system to select for membrane-tethered fluorescent proteins. Also in this issue, Hampel et al. report a similar strategy, Drosophila Brainbow, to select for epitope-tagged proteins detectable via immunofluorescence.
- Dafni Hadjieconomou
- , Shay Rotkopf
- & Iris Salecker
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Article |
Drosophila Brainbow: a recombinase-based fluorescence labeling technique to subdivide neural expression patterns
A genetic multicolor cell-labeling technique for Droshophila melanogaster, Drosophila Brainbow, is described and applied to the study of neural circuits. This method implements a variant of the mouse Brainbow strategy in combination with specific neuronal targeting using the Gal-4–upstream activating sequence system to select for epitope-tagged proteins detectable with immunofluorescence. Also in this issue, Hadjieconomou et al. develop a similar strategy, Flybow, to select for membrane-tethered fluorescent proteins.
- Stefanie Hampel
- , Phuong Chung
- & Julie H Simpson
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Resource |
A versatile in vivo system for directed dissection of gene expression patterns
A genetic platform allows refinement of tissue-specific expression using the upstream activating sequence–GAL4 system in Drosophila melanogaster, facilitating the segmentation of complex expression patterns and allowing GAL4 expression patterns to be repurposed.
- Daryl M Gohl
- , Marion A Silies
- & Thomas R Clandinin
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News & Views |
Unrestrained worms bridled by the light
Two systems allow precise optogenetic stimulation of specific neurons in freely behaving nematodes.
- André E X Brown
- & William R Schafer
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Article |
Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans
An optogenetic illumination system based on the use of a digital micromirror device and video tracking software is reported, which allows real-time light delivery with high spatial resolution to specified targets in freely moving Caenorhabditis elegans. Also in this issue, Stirman et al. report a similar illumination system using a liquid crystal display projector. Both methods allow optogenetic perturbation of a variety of neural circuits in the behaving worm.
- Andrew M Leifer
- , Christopher Fang-Yen
- & Aravinthan D T Samuel
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Article |
Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans
An optogenetic illumination system based on the use of a liquid crystal display projector and video tracking software is reported, which allows real-time multispectral light delivery with high spatial resolution to specified targets in freely moving Caenorhabditis elegans. Also in this issue, Leifer et al. report a similar illumination system using a digital micromirror device. Both methods allow optogenetic perturbation of a variety of neural circuits in the behaving worm.
- Jeffrey N Stirman
- , Matthew M Crane
- & Hang Lu
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Brief Communication |
Simultaneous two-photon calcium imaging at different depths with spatiotemporal multiplexing
In vivo calcium imaging at multiple depths simultaneously is shown using multifocal two-photon microscopy and spatiotemporal multiplexing. This technique involves scanning the sample with multiple beams in parallel at different axial planes and is applied to monitor neuronal network activity in multiple cortical layers of an anesthetized mouse.
- Adrian Cheng
- , J Tiago Gonçalves
- & Carlos Portera-Cailliau
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Research Highlights |
Unraveling synapse diversity
Array tomography opens the door to the large-scale exploration of molecular diversity of individual brain synapses.
- Erika Pastrana
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Commentary |
From cudgel to scalpel: toward precise neural control with optogenetics
Optogenetics is routinely used to activate and inactivate genetically defined neuronal populations in vivo. A second optogenetic revolution will occur when spatially distributed and sparse neural assemblies can be precisely manipulated in behaving animals.
- Simon Peron
- & Karel Svoboda
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Commentary |
Optogenetics
Optogenetics is a technology that allows targeted, fast control of precisely defined events in biological systems as complex as freely moving mammals. By delivering optical control at the speed (millisecond-scale) and with the precision (cell type–specific) required for biological processing, optogenetic approaches have opened new landscapes for the study of biology, both in health and disease.
- Karl Deisseroth
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News Feature |
Light tools
Optogenetics grows from an idea into a discipline. Monya Baker reports.
- Monya Baker
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Research Highlights |
Neuroscience in a virtual world
Using a virtual reality setup and a deep window into the brain, researchers can image the activity of neurons as mice navigate virtual environments.
- Erika Pastrana
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Editorial |
Brain observations
New tools are improving the prospects for transcranial light-based neuroscience, but better methods for using them are needed before they can reach their full potential.
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Technology Feature |
From promising to practical: tools to study networks of neurons
Combinations of electrophysiology, two-photon microscopy and new tools for detecting neural activity show how neurons function in circuits.
- Monya Baker
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Research Highlights |
Reading cells from within
A nanoscale field-effect transistor with a three-dimensional probe-presentation design can record intracellular potentials from single cells.
- Erika Pastrana
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News & Views |
Optogenetics meets optical wavefront shaping
Optogenetic stimulation by ultrashort laser pulses could allow neural circuits in the living brain to be probed with cellular resolution, despite pervasive light scattering. Now sophisticated new multiphoton stimulation systems that strike a better balance between lateral and axial resolution help realize this potential by matching the illumination volume to the soma's dimensions.
- Shy Shoham
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Resource |
Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents
This resource provides a comprehensive evaluation of rodent locomotor profiles after different types of lesions to the central nervous system. The data set can guide the selection of suitable lesion paradigms, locomotor tasks and readouts in future animal studies.
- Björn Zörner
- , Linard Filli
- & Martin E Schwab
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This Month |
Thomas Knöpfel
Linked fluorescent proteins are used to visualize voltage in living mouse brains.
- Monya Baker
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