title: Defective response inhibition and collicular noradrenaline enrichment in mice with duplicated retinotopic map in the superior colliculus.
abstract: 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.
authors.affiliation: Laboratory of Adaptative and Cognitive Neurosciences, CNRS, University of Strasbourg UMR 7364, 67000, Strasbourg, France, chantal.mathis@linc.u-strasbg.fr.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathis
authors.forename: Elise
authors.initials: E
authors.lastname: Savier
authors.forename: Jean-Bastien
authors.initials: JB
authors.lastname: Bott
authors.forename: Daniel
authors.initials: D
authors.lastname: Clesse
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bevins
authors.forename: Dominique
authors.initials: D
authors.lastname: Sage-Ciocca
authors.forename: Karin
authors.initials: K
authors.lastname: Geiger
authors.forename: Anaïs
authors.initials: A
authors.lastname: Gillet
authors.forename: Alexis
authors.initials: A
authors.lastname: Laux-Biehlmann
authors.forename: Yannick
authors.initials: Y
authors.lastname: Goumon
authors.forename: Adrien
authors.initials: A
authors.lastname: Lacaud
authors.forename: Vincent
authors.initials: V
authors.lastname: Lelièvre
authors.forename: Christian
authors.initials: C
authors.lastname: Kelche
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cassel
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
authors.forename: Michael
authors.initials: M
authors.lastname: Reber
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D002940:Circadian Rhythm; D003867:Depth Perception / Q000502:physiology; D004298:Dopamine / Q000032:analysis; D055879:Gene Knock-In Techniques; D007266:Inhibition, Psychological; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D008297:Male; D008568:Memory / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity; D009638:Norepinephrine / Q000032:analysis*; D011597:Psychomotor Performance / Q000502:physiology*; D036121:Receptor, EphA3 / Q000235:genetics; D013477:Superior Colliculi / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D014795:Visual Pathways / Q000502:physiology
chemical_list: C558561:Isl2 protein, mouse; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3; D004298:Dopamine; D009638:Norepinephrine