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  1. AU="Severi, Kristen E"
  2. AU="Robotti, Marzia"
  3. AU="Kaspar, Charles W"
  4. AU="Wallach, E E"
  5. AU="Temnikov, P"
  6. AU="Gomez-Verjan, Juan Carlos"
  7. AU="Mayle, Francis E."
  8. AU="Rhoades, Elizabeth"
  9. AU="Riaz, Huma"
  10. AU="Eliseu, Gabriel"
  11. AU="Hill, Lori R"
  12. AU="Boppana, Suresh B"

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  1. Artikel ; Online: Motor behavior: A feedforward circuit for zebrafish escape.

    Christie, Kevin W / Severi, Kristen E

    Current biology : CB

    2021  Band 31, Heft 15, Seite(n) R965–R967

    Abstract: A recent study of motor control in zebrafish demonstrates the critical role of an excitatory neural relay network in the transformation of a unilateral turn command into a subsequent bilateral swim signal. A rapid and smooth transition between these ... ...

    Abstract A recent study of motor control in zebrafish demonstrates the critical role of an excitatory neural relay network in the transformation of a unilateral turn command into a subsequent bilateral swim signal. A rapid and smooth transition between these motor phases is critical for successfully escaping danger.
    Mesh-Begriff(e) Animals ; Swimming ; Zebrafish
    Sprache Englisch
    Erscheinungsdatum 2021-08-10
    Erscheinungsland England
    Dokumenttyp Journal Article ; Comment
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2021.06.032
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  2. Artikel ; Online: Resilience of neural networks for locomotion.

    Haspel, Gal / Severi, Kristen E / Fauci, Lisa J / Cohen, Netta / Tytell, Eric D / Morgan, Jennifer R

    The Journal of physiology

    2021  Band 599, Heft 16, Seite(n) 3825–3840

    Abstract: Locomotion is an essential behaviour for the survival of all animals. The neural circuitry underlying locomotion is therefore highly robust to a wide variety of perturbations, including injury and abrupt changes in the environment. In the short term, ... ...

    Abstract Locomotion is an essential behaviour for the survival of all animals. The neural circuitry underlying locomotion is therefore highly robust to a wide variety of perturbations, including injury and abrupt changes in the environment. In the short term, fault tolerance in neural networks allows locomotion to persist immediately after mild to moderate injury. In the longer term, in many invertebrates and vertebrates, neural reorganization including anatomical regeneration can restore locomotion after severe perturbations that initially caused paralysis. Despite decades of research, very little is known about the mechanisms underlying locomotor resilience at the level of the underlying neural circuits and coordination of central pattern generators (CPGs). Undulatory locomotion is an ideal behaviour for exploring principles of circuit organization, neural control and resilience of locomotion, offering a number of unique advantages including experimental accessibility and modelling tractability. In comparing three well-characterized undulatory swimmers, lampreys, larval zebrafish and Caenorhabditis elegans, we find similarities in the manifestation of locomotor resilience. To advance our understanding, we propose a comparative approach, integrating experimental and modelling studies, that will allow the field to begin identifying shared and distinct solutions for overcoming perturbations to persist in orchestrating this essential behaviour.
    Mesh-Begriff(e) Animals ; Lampreys ; Locomotion ; Neural Networks, Computer ; Spinal Cord ; Zebrafish
    Sprache Englisch
    Erscheinungsdatum 2021-07-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3115-x
    ISSN 1469-7793 ; 0022-3751
    ISSN (online) 1469-7793
    ISSN 0022-3751
    DOI 10.1113/JP279214
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Investigation of hindbrain activity during active locomotion reveals inhibitory neurons involved in sensorimotor processing.

    Severi, Kristen E / Böhm, Urs L / Wyart, Claire

    Scientific reports

    2018  Band 8, Heft 1, Seite(n) 13615

    Abstract: Locomotion in vertebrates relies on motor circuits in the spinal cord receiving inputs from the hindbrain to execute motor commands while dynamically integrating proprioceptive sensory feedback. The spatial organization of the neuronal networks driving ... ...

    Abstract Locomotion in vertebrates relies on motor circuits in the spinal cord receiving inputs from the hindbrain to execute motor commands while dynamically integrating proprioceptive sensory feedback. The spatial organization of the neuronal networks driving locomotion in the hindbrain and role of inhibition has not been extensively investigated. Here, we mapped neuronal activity with single-cell resolution in the hindbrain of restrained transgenic Tg(HuC:GCaMP5G) zebrafish larvae swimming in response to whole-field visual motion. We combined large-scale population calcium imaging in the hindbrain with simultaneous high-speed recording of the moving tail in animals where specific markers label glycinergic inhibitory neurons. We identified cells whose activity preferentially correlates with the visual stimulus or motor activity and used brain registration to compare data across individual larvae. We then morphed calcium imaging data onto the zebrafish brain atlas to compare with known transgenic markers. We report cells localized in the cerebellum whose activity is shut off by the onset of the visual stimulus, suggesting these cells may be constitutively active and silenced during sensorimotor processing. Finally, we discover that the activity of a medial stripe of glycinergic neurons in the domain of expression of the transcription factor engrailed1b is highly correlated with the onset of locomotion. Our efforts provide a high-resolution, open-access dataset for the community by comparing our functional map of the hindbrain to existing open-access atlases and enabling further investigation of this population's role in locomotion.
    Mesh-Begriff(e) Animals ; Animals, Genetically Modified/genetics ; Animals, Genetically Modified/physiology ; Brain/physiology ; Larva/genetics ; Larva/physiology ; Locomotion/physiology ; Motor Activity/genetics ; Motor Activity/physiology ; Neurons/physiology ; Psychomotor Performance/physiology ; Rhombencephalon/physiology ; Sensorimotor Cortex/physiology ; Single-Cell Analysis ; Spinal Cord/physiology ; Swimming ; Zebrafish
    Sprache Englisch
    Erscheinungsdatum 2018-09-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-31968-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Evolutionary and homeostatic changes in morphology of visual dendrites of Mauthner cells in Astyanax blind cavefish.

    Tanvir, Zainab / Rivera, Daihana / Severi, Kristen E / Haspel, Gal / Soares, Daphne

    The Journal of comparative neurology

    2020  Band 529, Heft 8, Seite(n) 1779–1786

    Abstract: Mauthner cells are the largest neurons in the hindbrain of teleost fish and most amphibians. Each cell has two major dendrites thought to receive segregated streams of sensory input: the lateral dendrite receives mechanosensory input while the ventral ... ...

    Abstract Mauthner cells are the largest neurons in the hindbrain of teleost fish and most amphibians. Each cell has two major dendrites thought to receive segregated streams of sensory input: the lateral dendrite receives mechanosensory input while the ventral dendrite receives visual input. These inputs, which mediate escape responses to sudden stimuli, may be modulated by the availability of sensory information to the animal. To understand the impact of the absence of visual information on the morphologies of Mauthner cells during developmental and evolutionary time scales, we examined the teleost Astyanax mexicanus. This species of tetra is found in two morphs: a seeing surface fish and a blind cavefish. We compared the structure of Mauthner cells in surface fish raised under daily light conditions, in surface fish raised in constant darkness, and in two independent lineages of cave populations. The length of ventral dendrites of Mauthner cells in dark-raised surface fish larvae were longer and more branched, while in both cave morphs the ventral dendrites were smaller or absent. The absence of visual input in surface fish with normal eye development leads to a homeostatic increase in dendrite size, whereas over evolution, the absence of light led to the loss of eyes and a reduction in dendrite size.
    Mesh-Begriff(e) Adaptation, Physiological/physiology ; Animals ; Biological Evolution ; Characidae/anatomy & histology ; Darkness ; Dendrites/ultrastructure ; Homeostasis/physiology ; Neurogenesis/physiology
    Sprache Englisch
    Erscheinungsdatum 2020-10-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 3086-7
    ISSN 1096-9861 ; 0021-9967 ; 0092-7317
    ISSN (online) 1096-9861
    ISSN 0021-9967 ; 0092-7317
    DOI 10.1002/cne.25056
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel: ZebraZoom: an automated program for high-throughput behavioral analysis and categorization.

    Mirat, Olivier / Sternberg, Jenna R / Severi, Kristen E / Wyart, Claire

    Frontiers in neural circuits

    2013  Band 7, Seite(n) 107

    Abstract: The zebrafish larva stands out as an emergent model organism for translational studies involving gene or drug screening thanks to its size, genetics, and permeability. At the larval stage, locomotion occurs in short episodes punctuated by periods of rest. ...

    Abstract The zebrafish larva stands out as an emergent model organism for translational studies involving gene or drug screening thanks to its size, genetics, and permeability. At the larval stage, locomotion occurs in short episodes punctuated by periods of rest. Although phenotyping behavior is a key component of large-scale screens, it has not yet been automated in this model system. We developed ZebraZoom, a program to automatically track larvae and identify maneuvers for many animals performing discrete movements. Our program detects each episodic movement and extracts large-scale statistics on motor patterns to produce a quantification of the locomotor repertoire. We used ZebraZoom to identify motor defects induced by a glycinergic receptor antagonist. The analysis of the blind mutant atoh7 revealed small locomotor defects associated with the mutation. Using multiclass supervised machine learning, ZebraZoom categorized all episodes of movement for each larva into one of three possible maneuvers: slow forward swim, routine turn, and escape. ZebraZoom reached 91% accuracy for categorization of stereotypical maneuvers that four independent experimenters unanimously identified. For all maneuvers in the data set, ZebraZoom agreed with four experimenters in 73.2-82.5% of cases. We modeled the series of maneuvers performed by larvae as Markov chains and observed that larvae often repeated the same maneuvers within a group. When analyzing subsequent maneuvers performed by different larvae, we found that larva-larva interactions occurred as series of escapes. Overall, ZebraZoom reached the level of precision found in manual analysis but accomplished tasks in a high-throughput format necessary for large screens.
    Mesh-Begriff(e) Algorithms ; Animals ; Automation, Laboratory/methods ; Automation, Laboratory/standards ; Larva ; Motor Activity/physiology ; Swimming/physiology ; Video Recording/methods ; Video Recording/standards ; Zebrafish/physiology
    Sprache Englisch
    Erscheinungsdatum 2013-06-12
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2452968-0
    ISSN 1662-5110
    ISSN 1662-5110
    DOI 10.3389/fncir.2013.00107
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Optogenetics in a transparent animal: circuit function in the larval zebrafish.

    Portugues, Ruben / Severi, Kristen E / Wyart, Claire / Ahrens, Misha B

    Current opinion in neurobiology

    2013  Band 23, Heft 1, Seite(n) 119–126

    Abstract: Optogenetic tools can be used to manipulate neuronal activity in a reversible and specific manner. In recent years, such methods have been applied to uncover causal relationships between activity in specified neuronal circuits and behavior in the larval ... ...

    Abstract Optogenetic tools can be used to manipulate neuronal activity in a reversible and specific manner. In recent years, such methods have been applied to uncover causal relationships between activity in specified neuronal circuits and behavior in the larval zebrafish. In this small, transparent, genetic model organism, noninvasive manipulation and monitoring of neuronal activity with light is possible throughout the nervous system. Here we review recent work in which these new tools have been applied to zebrafish, and discuss some of the existing challenges of these approaches.
    Mesh-Begriff(e) Animals ; Behavior, Animal/physiology ; Brain/physiology ; Larva ; Optogenetics/methods ; Zebrafish/physiology
    Sprache Englisch
    Erscheinungsdatum 2013-02
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2012.11.001
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Neural control and modulation of swimming speed in the larval zebrafish.

    Severi, Kristen E / Portugues, Ruben / Marques, João C / O'Malley, Donald M / Orger, Michael B / Engert, Florian

    Neuron

    2014  Band 83, Heft 3, Seite(n) 692–707

    Abstract: Vertebrate locomotion at different speeds is driven by descending excitatory connections to central pattern generators in the spinal cord. To investigate how these inputs determine locomotor kinematics, we used whole-field visual motion to drive ... ...

    Abstract Vertebrate locomotion at different speeds is driven by descending excitatory connections to central pattern generators in the spinal cord. To investigate how these inputs determine locomotor kinematics, we used whole-field visual motion to drive zebrafish to swim at different speeds. Larvae match the stimulus speed by utilizing more locomotor events, or modifying kinematic parameters such as the duration and speed of swimming bouts, the tail-beat frequency, and the choice of gait. We used laser ablations, electrical stimulation, and activity recordings in descending neurons of the nucleus of the medial longitudinal fasciculus (nMLF) to dissect their contribution to controlling forward movement. We found that the activity of single identified neurons within the nMLF is correlated with locomotor kinematics, and modulates both the duration and oscillation frequency of tail movements. By identifying the contribution of individual supraspinal circuit elements to locomotion kinematics, we build a better understanding of how the brain controls movement.
    Mesh-Begriff(e) Animals ; Electric Stimulation/methods ; Larva/physiology ; Locomotion/physiology ; Motor Activity/physiology ; Nerve Net/physiology ; Neurons/physiology ; Spinal Cord/physiology ; Swimming/physiology ; Time Factors ; Zebrafish/physiology
    Sprache Englisch
    Erscheinungsdatum 2014-07-24
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2014.06.032
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  8. Artikel ; Online: Optimization of a Neurotoxin to Investigate the Contribution of Excitatory Interneurons to Speed Modulation In Vivo.

    Sternberg, Jenna R / Severi, Kristen E / Fidelin, Kevin / Gomez, Johanna / Ihara, Hideshi / Alcheikh, Yara / Hubbard, Jeffrey M / Kawakami, Koichi / Suster, Maximiliano / Wyart, Claire

    Current biology : CB

    2016  Band 26, Heft 17, Seite(n) 2319–2328

    Abstract: Precise control of speed during locomotion is essential for adaptation of behavior in different environmental contexts [1-4]. A central question in locomotion lies in understanding which neural populations set locomotor frequency during slow and fast ... ...

    Abstract Precise control of speed during locomotion is essential for adaptation of behavior in different environmental contexts [1-4]. A central question in locomotion lies in understanding which neural populations set locomotor frequency during slow and fast regimes. Tackling this question in vivo requires additional non-invasive tools to silence large populations of neurons during active locomotion. Here we generated a stable transgenic line encoding a zebrafish-optimized botulinum neurotoxin light chain fused to GFP (BoTxBLC-GFP) to silence synaptic output over large populations of motor neurons or interneurons while monitoring active locomotion. By combining calcium imaging, electrophysiology, optogenetics, and behavior, we show that expression of BoTxBLC-GFP abolished synaptic release while maintaining characterized activity patterns and without triggering off-target effects. As chx10(+) V2a interneurons (V2as) are well characterized as the main population driving the frequency-dependent recruitment of motor neurons during fictive locomotion [5-14], we validated our silencing method by testing the effect of silencing chx10(+) V2as during active and fictive locomotion. Silencing of V2as selectively abolished fast locomotor frequencies during escape responses. In addition, spontaneous slow locomotion occurred less often and at frequencies lower than in controls. Overall, this silencing approach confirms that V2a excitation is critical for the production of fast stimulus-evoked swimming and also reveals a role for V2a excitation in the production of slower spontaneous locomotor behavior. Altogether, these results establish BoTxBLC-GFP as an ideal tool for in vivo silencing for probing the development and function of neural circuits from the synaptic to the behavioral level.
    Mesh-Begriff(e) Animals ; Animals, Genetically Modified/embryology ; Animals, Genetically Modified/growth & development ; Animals, Genetically Modified/physiology ; Botulinum Toxins/pharmacology ; Embryo, Nonmammalian/drug effects ; Embryo, Nonmammalian/physiology ; Interneurons/physiology ; Locomotion/drug effects ; Locomotion/physiology ; Neurotoxins/pharmacology ; Swimming/physiology ; Zebrafish/embryology ; Zebrafish/growth & development ; Zebrafish/physiology
    Chemische Substanzen Neurotoxins ; Botulinum Toxins (EC 3.4.24.69)
    Sprache Englisch
    Erscheinungsdatum 2016-08-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1071731-6
    ISSN 1879-0445 ; 0960-9822
    ISSN (online) 1879-0445
    ISSN 0960-9822
    DOI 10.1016/j.cub.2016.06.037
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Control of visually guided behavior by distinct populations of spinal projection neurons.

    Orger, Michael B / Kampff, Adam R / Severi, Kristen E / Bollmann, Johann H / Engert, Florian

    Nature neuroscience

    2008  Band 11, Heft 3, Seite(n) 327–333

    Abstract: A basic question in the field of motor control is how different actions are represented by activity in spinal projection neurons. We used a new behavioral assay to identify visual stimuli that specifically drive basic motor patterns in zebrafish. These ... ...

    Abstract A basic question in the field of motor control is how different actions are represented by activity in spinal projection neurons. We used a new behavioral assay to identify visual stimuli that specifically drive basic motor patterns in zebrafish. These stimuli evoked consistent patterns of neural activity in the neurons projecting to the spinal cord, which we could map throughout the entire population using in vivo two-photon calcium imaging. We found that stimuli that drive distinct behaviors activated distinct subsets of projection neurons, consisting, in some cases, of just a few cells. This stands in contrast to the distributed activation seen for more complex behaviors. Furthermore, targeted cell by cell ablations of the neurons associated with evoked turns abolished the corresponding behavioral response. This description of the functional organization of the zebrafish motor system provides a framework for identifying the complete circuit underlying a vertebrate behavior.
    Mesh-Begriff(e) Action Potentials/physiology ; Animals ; Axons/physiology ; Axons/ultrastructure ; Brain Stem/anatomy & histology ; Brain Stem/physiology ; Calcium/chemistry ; Denervation ; Efferent Pathways/anatomy & histology ; Efferent Pathways/physiology ; Fluorescent Dyes ; Functional Laterality/physiology ; Indicators and Reagents ; Locomotion/physiology ; Models, Animal ; Nerve Net/cytology ; Nerve Net/physiology ; Neurons/cytology ; Neurons/physiology ; Orientation/physiology ; Psychomotor Performance/physiology ; Reticular Formation/anatomy & histology ; Reticular Formation/physiology ; Spinal Cord/anatomy & histology ; Spinal Cord/physiology ; Staining and Labeling ; Swimming/physiology ; Visual Pathways/physiology ; Zebrafish/anatomy & histology ; Zebrafish/physiology
    Chemische Substanzen Fluorescent Dyes ; Indicators and Reagents ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2008-02-10
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1420596-8
    ISSN 1546-1726 ; 1097-6256
    ISSN (online) 1546-1726
    ISSN 1097-6256
    DOI 10.1038/nn2048
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics.

    Akerboom, Jasper / Carreras Calderón, Nicole / Tian, Lin / Wabnig, Sebastian / Prigge, Matthias / Tolö, Johan / Gordus, Andrew / Orger, Michael B / Severi, Kristen E / Macklin, John J / Patel, Ronak / Pulver, Stefan R / Wardill, Trevor J / Fischer, Elisabeth / Schüler, Christina / Chen, Tsai-Wen / Sarkisyan, Karen S / Marvin, Jonathan S / Bargmann, Cornelia I /
    Kim, Douglas S / Kügler, Sebastian / Lagnado, Leon / Hegemann, Peter / Gottschalk, Alexander / Schreiter, Eric R / Looger, Loren L

    Frontiers in molecular neuroscience

    2013  Band 6, Seite(n) 2

    Abstract: Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, "RCaMPs," engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution ... ...

    Abstract Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, "RCaMPs," engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca(2+)-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca(2+)]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca(2+) affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.
    Sprache Englisch
    Erscheinungsdatum 2013-03-04
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2452967-9
    ISSN 1662-5099
    ISSN 1662-5099
    DOI 10.3389/fnmol.2013.00002
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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