caa a22 4500 606202366 CHVBK 20210128100952.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00429-014-0745-5 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0745-5 Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus [Elektronische Daten] [Chantal Mathis, Elise Savier, Jean-Bastien Bott, Daniel Clesse, Nicholas Bevins, Dominique Sage-Ciocca, Karin Geiger, Anaïs Gillet, Alexis Laux-Biehlmann, Yannick Goumon, Adrien Lacaud, Vincent Lelièvre, Christian Kelche, Jean-Christophe Cassel, Frank Pfrieger, Michael Reber] The superior colliculus is a hub for multisensory integration necessary for visuo-spatial orientation, control of gaze movements and attention. The multiple functions of the superior colliculus have prompted hypotheses about its involvement in neuropsychiatric conditions, but to date, this topic has not been addressed experimentally. We describe experiments on genetically modified mice, the Isl2-EphA3 knock-in line, that show a well-characterized duplication of the retino-collicular and cortico-collicular axonal projections leading to hyperstimulation of the superior colliculus. To explore the functional impact of collicular hyperstimulation, we compared the performance of homozygous knock-in, heterozygous knock-in and wild-type mice in several behavioral tasks requiring collicular activity. The light/dark box test and Go/No-Go conditioning task revealed that homozygous mutant mice exhibit defective response inhibition, a form of impulsivity. This defect was specific to attention as other tests showed no differences in visually driven behavior, motivation, visuo-spatial learning and sensorimotor abilities among the different groups of mice. Monoamine quantification and gene expression profiling demonstrated a specific enrichment of noradrenaline only in the superficial layers of the superior colliculus of Isl2-EphA3 knock-in mice, where the retinotopy is duplicated, whereas transcript levels of receptors, transporters and metabolic enzymes of the monoaminergic pathway were not affected. We demonstrate that the defect in response inhibition is a consequence of noradrenaline imbalance in the superficial layers of the superior colliculus caused by retinotopic map duplication. Our results suggest that structural abnormalities in the superior colliculus can cause defective response inhibition, a key feature of attention-deficit disorders. The Author(s), 2014 Retinotopy nationallicence Visual system nationallicence EphA signaling nationallicence Superior colliculus nationallicence Noradrenaline nationallicence Response inhibition nationallicence Attention-deficit disorders nationallicence Mathis Chantal Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Savier Elise Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Bott Jean-Bastien Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Clesse Daniel Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Bevins Nicholas Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, 92037, San Diego, CA, USA aut Sage-Ciocca Dominique Chronobiotron, UMS 3415, CNRS, 67084, Strasbourg, France aut Geiger Karin Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Gillet Anaïs Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Laux-Biehlmann Alexis Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Goumon Yannick Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Lacaud Adrien Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Lelièvre Vincent Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Kelche Christian Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Cassel Jean-Christophe Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut Pfrieger Frank Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Reber Michael Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1573-1584 1863-2653 220:3<1573 2015 220 429 https://doi.org/10.1007/s00429-014-0745-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0745-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mathis Chantal Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Savier Elise Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Bott Jean-Bastien Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Clesse Daniel Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Bevins Nicholas Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, 92037, San Diego, CA, USA aut NATIONALLICENCE 700 1- Sage-Ciocca Dominique Chronobiotron, UMS 3415, CNRS, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Geiger Karin Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Gillet Anaïs Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Laux-Biehlmann Alexis Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Goumon Yannick Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Lacaud Adrien Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Lelièvre Vincent Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Kelche Christian Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Cassel Jean-Christophe Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France aut NATIONALLICENCE 700 1- Pfrieger Frank Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 700 1- Reber Michael Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5, rue blaise Pascal, 67084, Strasbourg, France aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1573-1584 1863-2653 220:3<1573 2015 220 429