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Author

Yi Sun

Bio: Yi Sun is an academic researcher from Howard Hughes Medical Institute. The author has contributed to research in topics: Calcium imaging & Lab-on-a-chip. The author has an hindex of 16, co-authored 28 publications receiving 6151 citations. Previous affiliations of Yi Sun include Beijing University of Technology & Chinese Academy of Sciences.

Papers
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Journal ArticleDOI
18 Jul 2013-Nature
TL;DR: A family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo are developed and provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
Abstract: Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.

5,365 citations

Journal ArticleDOI
24 Mar 2016-eLife
TL;DR: Improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a) are presented, with sensitivity comparable to GCaMP6, to facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging.
Abstract: Neurons encode information with brief electrical pulses called spikes. Monitoring spikes in large populations of neurons is a powerful method for studying how networks of neurons process information and produce behavior. This activity can be detected using fluorescent protein indicators, or “probes”, which light up when neurons are active. The best existing probes produce green fluorescence. However, red fluorescent probes would allow us to see deeper into the brain, and could also be used with green probes to image the activity and interactions of different neuron types simultaneously. However, existing red fluorescent probes are not as good at detecting neural activity as green probes. By optimizing two existing red fluorescent proteins, Dana et al. have now produced two new red fluorescent probes, each with different advantages. The new protein indicators detect neural activity with high sensitivity and allow researchers to image previously unseen brain activity. Tests showed that the probes work in cultured neurons and allow imaging of the activity of neurons in mice, flies, fish and worms. History has shown that enhancing the techniques used to study biological processes can lead to fundamentally new insights. In the future, Dana et al. would therefore like to make even more sensitive protein indicators that will allow larger networks of neurons deeper in the brain to be imaged.

762 citations

Journal ArticleDOI
TL;DR: The ‘jGCaMP7’ sensors are four genetically encoded calcium indicators with better sensitivity than state-of-the-art GCaMP6 and specifically improved for applications such as neuropil or wide-field imaging.
Abstract: 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 activity in large populations of neuronal cell bodies, or to follow dynamics in subcellular compartments such as axons, dendrites and individual synaptic compartments. Despite major advances, calcium imaging is still limited by the biophysical properties of existing GECIs, including affinity, signal-to-noise ratio, rise and decay kinetics and dynamic range. Using structure-guided mutagenesis and neuron-based screening, we optimized the green fluorescent protein-based GECI GCaMP6 for different modes of in vivo imaging. The resulting jGCaMP7 sensors provide improved detection of individual spikes (jGCaMP7s,f), imaging in neurites and neuropil (jGCaMP7b), and may allow tracking larger populations of neurons using two-photon (jGCaMP7s,f) or wide-field (jGCaMP7c) imaging.

723 citations

Journal ArticleDOI
13 Feb 2015-Science
TL;DR: A fluorescent sensor, CaMPARI, is designed that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise “activity snapshot” of a large tissue volume.
Abstract: The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca(2+)) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise "activity snapshot" of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca(2+) and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies.

366 citations

Journal ArticleDOI
TL;DR: The fabrication of tubular structures, with multiple cell types forming different layers of the tube walls, is described using a stress-induced rolling membrane (SIRM).
Abstract: The fabrication of tubular structures, with multiple cell types forming different layers of the tube walls, is described using a stress-induced rolling membrane (SIRM). Cell orientation inside the tubes can also be controlled by topographical contact guidance. These layered tubes precisely mimic blood vessels and many other tubular structures, suggesting that they may be of great use in tissue engineering.

225 citations


Cited by
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Journal ArticleDOI
TL;DR: This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.
Abstract: Decades of research has identified the brain areas that are involved in fear, fear extinction, anxiety and related defensive behaviours. Newly developed genetic and viral tools, optogenetics and advanced in vivo imaging techniques have now made it possible to characterize the activity, connectivity and function of specific cell types within complex neuronal circuits. Recent findings that have been made using these tools and techniques have provided mechanistic insights into the exquisite organization of the circuitry underlying internal defensive states. This Review focuses on studies that have used circuit-based approaches to gain a more detailed, and also more comprehensive and integrated, view on how the brain governs fear and anxiety and how it orchestrates adaptive defensive behaviours.

1,223 citations

Journal ArticleDOI
19 Jun 2014-Cell
TL;DR: Fiber photometry was developed and applied to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior and captures a fundamental and previously inaccessible dimension of mammalian circuit dynamics.

1,064 citations

Journal ArticleDOI
04 Mar 2015-Neuron
TL;DR: These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity, and develop driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems.

929 citations

Journal ArticleDOI
19 Oct 2016-Neuron
TL;DR: A newly evolved variant of adeno-associated virus, rAAV2-retro, permits robust retrograde access to projection neurons with efficiency comparable to classical synthetic retrograde tracers and enables sufficient sensor/effector expression for functional circuit interrogation and in vivo genome editing in targeted neuronal populations.

925 citations

Journal ArticleDOI
20 Jan 2016-Neuron
TL;DR: This work presents a modular approach for analyzing calcium imaging recordings of large neuronal ensembles that relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neurons in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time.

900 citations