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      Dendritic and parallel processing of visual threats in the retina control defensive responses

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          Abstract

          The dendrites of a retinal interneuron detect visual threats and initiate defensive responses through parallel pathways.

          Abstract

          Approaching predators cast expanding shadows (i.e., looming) that elicit innate defensive responses in most animals. Where looming is first detected and how critical parameters of predatory approaches are extracted are unclear. In mice, we identify a retinal interneuron (the VG3 amacrine cell) that responds robustly to looming, but not to related forms of motion. Looming-sensitive calcium transients are restricted to a specific layer of the VG3 dendrite arbor, which provides glutamatergic input to two ganglion cells (W3 and OFFα). These projection neurons combine shared excitation with dissimilar inhibition to signal approach onset and speed, respectively. Removal of VG3 amacrine cells reduces the excitation of W3 and OFFα ganglion cells and diminishes defensive responses of mice to looming without affecting other visual behaviors. Thus, the dendrites of a retinal interneuron detect visual threats, divergent circuits downstream extract critical threat parameters, and these retinal computations initiate an innate survival behavior.

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          A robust and high-throughput Cre reporting and characterization system for the whole mouse brain

          The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universal responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in a number of Cre-driver lines, including novel Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.
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            How inhibition shapes cortical activity.

            Cortical processing reflects the interplay of synaptic excitation and synaptic inhibition. Rapidly accumulating evidence is highlighting the crucial role of inhibition in shaping spontaneous and sensory-evoked cortical activity and thus underscores how a better knowledge of inhibitory circuits is necessary for our understanding of cortical function. We discuss current views of how inhibition regulates the function of cortical neurons and point to a number of important open questions. Copyright © 2011 Elsevier Inc. All rights reserved.
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              A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration.

              A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes cell ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for cell ablation in vivo.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                November 2020
                18 November 2020
                : 6
                : 47
                : eabc9920
                Affiliations
                [1 ]John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
                [2 ]Graduate Program in Neuroscience, Washington University School of Medicine, Saint Louis, MO 63110, USA.
                [3 ]Department of Neurosciences, Washington University School of Medicine, Saint Louis, MO 63110, USA.
                [4 ]Department of Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO 63110, USA.
                [5 ]Hope Center for Neurological Disorders, Washington University School of Medicine, Saint Louis, MO 63110, USA.
                Author notes
                [*]

                Present address: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.

                []Corresponding author. Email: kerschensteinerd@ 123456wustl.edu
                Author information
                http://orcid.org/0000-0001-8090-4269
                http://orcid.org/0000-0002-5268-9239
                http://orcid.org/0000-0002-6794-9056
                Article
                abc9920
                10.1126/sciadv.abc9920
                7673819
                33208370
                09df3744-c9f5-4f00-9d6b-6af2838ad809
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 25 May 2020
                : 01 October 2020
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY023341
                Funded by: doi http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY026978
                Funded by: doi http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY027411
                Funded by: doi http://dx.doi.org/10.13039/100000053, National Eye Institute;
                Award ID: EY030623
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Neurophysiology
                Neuroscience
                Neurophysiology
                Custom metadata
                Kyle Solis

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