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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 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
Direct wavefront sensing enables functional imaging of infragranular axons and spines
We advance two-photon microscopy for near-diffraction-limited imaging up to 850 µm below the pia in awake mice. Our approach combines direct wavefront sensing of light from a guidestar (formed by descanned flu...
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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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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
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 im...
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Engineering and Application of Genetically Encoded Calcium Indicators
Genetically encoded fluorescent biosensors are useful tools for tracking target analytes in cells, tissues and living organisms. These probes are often chimeric proteins consisting of a recognition element (e....
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Article
Recombinant approaches to IgG-like bispecific antibodies
One of the major obstacles in the development of bispecific antibodies (BsAb) has been the difficulty of producing the materials in sufficient quality and quantity by traditional technologies, such as the hybr...
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Article
Manipulation of ligand binding affinity by exploitation of conformational coupling
Traditional approaches for increasing the affinity of a protein for its ligand focus on constructing improved surface complementarity in the complex by altering the protein binding site to better fit the ligan...
