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| Open AccessRoboEM: automated 3D flight tracing for synaptic-resolution connectomics
RoboEM enables automated proofreading of electron microscopy datasets using a strategy akin to that of self-steering cars. This decreases the need for manual proofreading of segmented datasets and facilitates connectomic analyses.
- Martin Schmidt
- , Alessandro Motta
- & Moritz Helmstaedter
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Article |
Improved green and red GRAB sensors for monitoring spatiotemporal serotonin release in vivo
Deng et al. expand the toolbox of neurotransmitter sensors with high-sensitivity green and red genetically encoded serotonin sensors. These are suitable for in vivo applications, as demonstrated in a variety of applications in mice.
- Fei Deng
- , Jinxia Wan
- & Yulong Li
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Article |
Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo
Next-generation red and green G-protein-coupled receptor-based dopamine sensors with improved properties have been developed. Their performance is demonstrated in cell culture, in brain slices and in vivo in the mouse.
- Yizhou Zhuo
- , Bin Luo
- & Yulong Li
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Research Briefing |
Ultrafast nLight indicators for sensitive and specific in vivo imaging of norepinephrine
We developed, characterized and validated nLight sensors, a new family of genetically encoded green and red fluorescent norepinephrine indicators based on an alpha-1 adrenergic receptor. nLight probes can detect norepinephrine in living animals with superior sensitivity, ligand specificity and temporal resolution as compared with previous tools.
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Article |
Sensitive multicolor indicators for monitoring norepinephrine in vivo
Red and green genetically encoded indicators for norepinephrine have been developed and employed to monitor norepinephrine during locomotion and reward behavior in mice. The strategy used for generating these indicators also produced indicators for other neuromodulators.
- Zacharoula Kagiampaki
- , Valentin Rohner
- & Tommaso Patriarchi
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Brief Communication
| Open AccessHigh-contrast en bloc staining of mouse whole-brain and human brain samples for EM-based connectomics
For EM-based connectomics applications, a staining protocol for large tissue samples in the range of a centimeter has been developed, which avoids artifacts common with established protocols.
- Kun Song
- , Zhihui Feng
- & Moritz Helmstaedter
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Article
| Open AccessGlutamate indicators with improved activation kinetics and localization for imaging synaptic transmission
iGluSnFR variants with improved signal-to-noise ratios and targeting to postsynaptic sites have been developed, enabling the analysis of glutamatergic neurotransmission in vivo as illustrated in the mouse visual and somatosensory cortex.
- Abhi Aggarwal
- , Rui Liu
- & Kaspar Podgorski
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Research Briefing |
Photon-based communication between two neurons in Caenorhabditis elegans
Cells exchange information with one another using secreted chemicals as data carriers. We developed an all-optogenetic synaptic transmission system that replaced a chemical neurotransmitter with emitted photons. This system enabled synthetic signaling between unconnected neurons and the generation of prosthetic synaptic circuits.
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Article |
Neural engineering with photons as synaptic transmitters
PhAST is a technology for establishing de novo or modulating synaptic transmission in a light-dependent manner in C. elegans. By combining a calcium-dependent luciferase on pre-synapses with channelrhodopsin on post-synapses, light serves as a synthetic neurotransmitter.
- Montserrat Porta-de-la-Riva
- , Adriana Carolina Gonzalez
- & Michael Krieg
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Research Briefing |
Lighting up oxytocin dynamics in the brain with MTRIAOT
A genetically encoded green fluorescent sensor for oxytocin, MTRIAOT, offers an opportunity to perform real-time recording of brain oxytocin dynamics in living animals.
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Article
| Open AccessA fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain
A fluorescent sensor for oxytocin called MTRIAOT has been developed. The sensor’s capabilities are demonstrated in fiber photometry measurements in freely behaving mice.
- Daisuke Ino
- , Yudai Tanaka
- & Masaaki Nishiyama
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Article |
A genetically encoded sensor for in vivo imaging of orexin neuropeptides
OxLight1 is a genetically encoded sensor for the orexin neuropeptides. It has been applied in fiber photometry recordings and two-photon imaging in mice during a variety of behaviors.
- Loïc Duffet
- , Seher Kosar
- & Tommaso Patriarchi
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Brief Communication |
RETRACTED ARTICLE: A fast, high-affinity fluorescent serotonin biosensor engineered from a tick lipocalin
G-GESS is a serotonin biosensor, derived from a tick serotonin-binding protein. The biosensor has been applied here in cell culture, primary neurons, mouse brain slices and in vivo in the mouse brain.
- Shen Zhang
- , Xinyu Li
- & Hui-wang Ai
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Article |
Next-generation GRAB sensors for monitoring dopaminergic activity in vivo
Red and improved green versions of the genetically encoded dopamine sensor GRABDA have been developed. These neurotransmitter sensors are used alone or in combination with, for example, calcium sensors in behaving fruit flies and rodents.
- Fangmiao Sun
- , Jingheng Zhou
- & Yulong Li
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Article |
An optimized acetylcholine sensor for monitoring in vivo cholinergic activity
A genetically encoded acetylcholine sensor with improved sensitivity allows detection of cholinergic neurotransmission in vivo in the Drosophila and mouse brain.
- Miao Jing
- , Yuexuan Li
- & Yulong Li
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Article |
Kilohertz frame-rate two-photon tomography
A two-photon computed tomography approach, called scanned line angular projection microscopy, enables high-speed imaging at over 1 kHz frame rates, as demonstrated for glutamate imaging in the in vivo mouse brain.
- Abbas Kazemipour
- , Ondrej Novak
- & Kaspar Podgorski
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Article |
A genetically encoded fluorescent sensor for in vivo imaging of GABA
The genetically encoded GABA sensor iGABASnFR allows visualizing GABA signaling in vivo. Its application is demonstrated in mouse slices, in the awake mouse and in behaving zebrafish.
- Jonathan S. Marvin
- , Yoshiteru Shimoda
- & Loren L. Looger
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Brief Communication |
Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR
Variants of the genetically encoded sensor iGluSnFR extend the range of conditions under which glutamate neurotransmission can be visualized. In addition, chromatic variants of iGluSnFR improve compatibility with various illumination schemes.
- Jonathan S. Marvin
- , Benjamin Scholl
- & Loren L. Looger
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Article |
All-optical synaptic electrophysiology probes mechanism of ketamine-induced disinhibition
The synOptopatch approach enables all-optical access to synaptic communication via mutually exclusive expression of an optogenetic actuator and a voltage sensor in pre- and postsynaptic neurons, respectively.
- Linlin Z. Fan
- , Ralda Nehme
- & Adam E. Cohen
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Methods in Brief |
The proteomes of excitatory and inhibitory synaptic clefts
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This Month |
Don Arnold
To the tune of a classical guitar, finding a way to watch learning as it happens.
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Article |
An E3-ligase-based method for ablating inhibitory synapses
When studying neural circuitry, the ablation of synapses may be an alternative to optogenetic manipulation of neurons. A genetically encoded tool called GFE3 eliminates inhibitory inputs into neurons expressing GFE3.
- Garrett G Gross
- , Christoph Straub
- & Don B Arnold
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Tools in Brief |
Optimized tracing of neural circuits
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Tools in Brief |
A transformative tool for trans-synaptic tracing
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This Month |
David Kleinfeld
Measuring neurotransmitter concentration, letting lab meetings run free, and why biology does not own neuroscience.
- Vivien Marx
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Article |
Cell-based reporters reveal in vivo dynamics of dopamine and norepinephrine release in murine cortex
Cell-based reporters for dopamine and norepinephrine allow real-time measurements of these neurotransmitters in vivo with high specificity. They can address the temporal and spatial dynamics of volume neurotransmission in behaving animals.
- Arnaud Muller
- , Victory Joseph
- & David Kleinfeld
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Tools in Brief |
Flexible and minimally invasive nanowires
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Tools in Brief |
Synapses under the spotlight
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Tools in Brief |
Metabotropic receptors under the spotlight
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This Month |
Loren L. Looger
Engineering protein sensors to light up split-second signals in the brain
- Vivien Marx
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Article |
An optimized fluorescent probe for visualizing glutamate neurotransmission
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
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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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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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Article |
Silencing neurotransmission with membrane-tethered toxins
The use of membrane-tethered toxins to selectively block ion channel function in vivo is demonstrated. The approach is applied to blockade of voltage-gated calcium channels for inhibition of neurotransmission in the mouse.
- Sebastian Auer
- , Annika S Stürzebecher
- & Inés Ibañez-Tallon
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News & Views |
Advancing neurochemical monitoring
Two new approaches to neurochemical monitoring in vivo—an improved real-time microsensor and genetically engineered cells that sense neurotransmitter levels—address the critical issue of brain reactivity to implanted devices.
- Paul A Garris