Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance

By L. Madisen, Aleena R. Garner, Daisuke Shimaoka, A. Chuong, Nathan C. Klapoetke, Lu Li, A. Bourg, Y. Niino, Ladan Egolf, C. Monetti and 16 more. Neuron, 2015

1,048 citations recorded by the source corpus.

Summary An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems, and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.

Subfields: Biophysics, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bd6a00f49932432d80cede83a881ad349257d6d5

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Citations in the corpus

Shared cortex-cerebellum dynamics in the execution and learning of a motor task (2019, neutral): “Relating GrC Ca2+ transients to spiking Prior work imaging cerebellar granule cells with patch electrode recordings from the same cells in vitro estimated that 1 GrC action potential is likely associated with 15%Df/f GCaMP6f transients (Giovannucci et al., 2017).”
A Mammalian enhancer trap resource for discovering and manipulating neuronal cell types (2016, background): “…distal enhancers, BAC-transgenic (Gong et al., 2003; 2007) and knock-in (Taniguchi et al., 2011) approaches have been used to generate lines that copy expression patterns of targeted genes with high-fidelity, but many of these are quite broadly expressed (Harris et al., 2014; Madisen et al., 2015).”
Variance and invariance of neuronal long-term representations (2017, neutral): “Together with the large-‐scale efforts to map cellular activity chronically with regional and cell-‐type specificity [95] and constant improvements of our toolset to label and record from cell types defined by ”
Adult Mouse Cortical Cell Taxonomy by Single Cell Transcriptomics (2016, neutral): “For the full list of recombinase and reporter lines see Supplementary Table 1 19, 20, 32, 52–60 and Supplementary Table 2 56, 58 , respectively.”
A large field of view two-photon mesoscope with subcellular resolution for in vivo imaging (2016, background): “A fast (4.3 Hz), low-resolution scan across the entire scan range has up to 500 lines per stripe (iv).”
Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization (2017, neutral): “5-2 fold) than when Tir1 was inserted at Rosa26 or randomly (Figure S3C), suggesting that Tigre allows for higher expression or the Tir1 transgene, as reported previously (Madisen et al., 2015).”