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Open AccessMulticore fiber optic imaging reveals that astrocyte calcium activity in the mouse cerebral cortex is modulated by internal motivational state
Astrocytes are a direct target of neuromodulators and can influence neuronal activity on broad spatial and temporal scales in response to a rise in cytosolic calcium. However, our knowledge about how astrocyte...
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Visualization of Glutamatergic Neurotransmission in Diverse Model Organisms with Genetically Encoded Indicators
Glutamate is the principal excitatory neurotransmitter, and occasionally subserves inhibitory roles, in the vertebrate nervous system. Glutamatergic synapses are dense in the vertebrate brain, at ~1/μm3. Glutamat...
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Article
Open AccessGlutamate indicators with improved activation kinetics and localization for imaging synaptic transmission
The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing iGluSnFR variants exhibit low in vivo signal-to-noise ratios, saturat...
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Article
Open AccessFast and sensitive GCaMP calcium indicators for imaging neural populations
Calcium imaging with protein-based indicators1,2 is widely used to follow neural activity in intact nervous systems, but current protein sensors report neural activity at timescales much slower than electrical si...
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Article
Ketamine triggers a switch in excitatory neuronal activity across neocortex
The brain can become transiently disconnected from the environment while maintaining vivid, internally generated experiences. This so-called ‘dissociated state’ can occur in pathological conditions and under t...
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Article
Open AccessChemically stable fluorescent proteins for advanced microscopy
We report the rational engineering of a remarkably stable yellow fluorescent protein (YFP), ‘hyperfolder YFP’ (hfYFP), that withstands chaotropic conditions that denature most biological structures within seco...
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Article
Open AccessMany dissimilar NusG protein domains switch between α-helix and β-sheet folds
Folded proteins are assumed to be built upon fixed scaffolds of secondary structure, α-helices and β-sheets. Experimentally determined structures of >58,000 non-redundant proteins support this assumption, thou...
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Article
Open AccessThe functional organization of excitatory synaptic input to place cells
Hippocampal place cells contribute to mammalian spatial navigation and memory formation. Numerous models have been proposed to explain the location-specific firing of this cognitive representation, but the pat...
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Article
jYCaMP: an optimized calcium indicator for two-photon imaging at fiber laser wavelengths
Femtosecond lasers at fixed wavelengths above 1,000 nm are powerful, stable and inexpensive, making them promising sources for two-photon microscopy. Biosensors optimized for these wavelengths are needed for b...
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Article
Author Correction: Kilohertz frame-rate two-photon tomography
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
A genetically encoded fluorescent sensor for in vivo imaging of GABA
Current techniques for monitoring GABA (γ-aminobutyric acid), the primary inhibitory neurotransmitter in vertebrates, cannot follow transients in intact neural circuits. To develop a GABA sensor, we applied th...
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Article
Kilohertz frame-rate two-photon tomography
Point-scanning two-photon microscopy enables high-resolution imaging within scattering specimens such as the mammalian brain, but sequential acquisition of voxels fundamentally limits its speed. We developed a...
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Article
High-performance calcium sensors for imaging activity in neuronal populations and microcompartments
Calcium imaging with genetically encoded calcium indicators (GECIs) is routinely used to measure neural activity in intact nervous systems. GECIs are frequently used in one of two different modes: to track act...
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Article
Author Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR
The version of this paper originally published cited a preprint version of ref. 12 instead of the published version (Proc. Natl. Acad. Sci. USA 115, 5594–5599; 2018), which was available before this Nature Method...
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Article
Open AccessMultiplex imaging relates quantal glutamate release to presynaptic Ca2+ homeostasis at multiple synapses in situ
Information processing by brain circuits depends on Ca2+-dependent, stochastic release of the excitatory neurotransmitter glutamate. Whilst optical glutamate sensors have enabled detection of synaptic discharges,...
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Article
Open AccessA genetically encoded single-wavelength sensor for imaging cytosolic and cell surface ATP
Adenosine 5′ triphosphate (ATP) is a universal intracellular energy source and an evolutionarily ancient, ubiquitous extracellular signal in diverse species. Here, we report the generation and characterization...
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Publisher Correction: Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR
In the version of this paper originally published, important figure labels in Fig. 3d were not visible. An image layer present in the authors’ original figure that included two small dashed outlines and text l...
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Article
Stability, affinity, and chromatic variants of the glutamate sensor iGluSnFR
Single-wavelength fluorescent reporters allow visualization of specific neurotransmitters with high spatial and temporal resolution. We report variants of intensity-based glutamate-sensing fluorescent reporter...
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Article
Distinct descending motor cortex pathways and their roles in movement
Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer ...
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Article
Neural signatures of dynamic stimulus selection in Drosophila
Using two-color two-photon calcium imaging, the authors identified transformations of representations across synaptically connected pairs of neurons along a visual pathway to the Drosophila central complex. Neura...