Authors
Jess Nithianantharajah, Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration, The University of Edinburgh, Edinburgh, UK. Genes to Cognition Programme, The Wellcome Trust Sanger Institute, Hinxton, UK
Noboru H. Komiyama, Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration, The University of Edinburgh, Edinburgh, UK. Genes to Cognition Programme, The Wellcome Trust Sanger Institute, Hinxton, UK
Andrew McKechanie, Division of Psychiatry, The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. The Patrick Wild Centre, The University of Edinburgh, Edinburgh, UK
Mandy Johnstone, Division of Psychiatry, The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
Douglas H. Blackwood, Division of Psychiatry, The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK
David St.Clair, 5Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
Richard D. Emes, 6School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, UK
Louie N. van de Lagemaat, Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration, The University of Edinburgh, Edinburgh, UK. Genes to Cognition Programme, The Wellcome Trust Sanger Institute, Hinxton, UK
Lisa M. Saksida, Department of Experimental Psychology, University of Cambridge, Cambridge, UK. The Medical Research Council and The Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
Timothy J. Bussey, Department of Experimental Psychology, University of Cambridge, Cambridge, UK. The Medical Research Council and The Wellcome Trust Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
Seth G. Grant, Genes to Cognition Programme, Centre for Clinical Brain Sciences and Centre for Neuroregeneration, The University of Edinburgh, Edinburgh, UK. Genes to Cognition Programme, The Wellcome Trust Sanger Institute, Hinxton, UK
Journal
Nature Neuroscience
URL with Digital Object Identifier
10.1038/nn.3276
Abstract
The origins and evolution of higher cognitive functions, including complex forms of learning, attention and executive functions, are unknown. A potential mechanism driving the evolution of vertebrate cognition early in the vertebrate lineage (550 million years ago) was genome duplication and subsequent diversification of postsynaptic genes. Here we report, to our knowledge, the first genetic analysis of a vertebrate gene family in cognitive functions measured using computerized touchscreens. Comparison of mice carrying mutations in each of the four Dlg paralogs showed that simple associative learning required Dlg4, whereas Dlg2 and Dlg3 diversified to have opposing functions in complex cognitive processes. Exploiting the translational utility of touchscreens in humans and mice, testing Dlg2 mutations in both species showed that Dlg2's role in complex learning, cognitive flexibility and attention has been highly conserved over 100 million years. Dlg-family mutations underlie psychiatric disorders, suggesting that genome evolution expanded the complexity of vertebrate cognition at the cost of susceptibility to mental illness.
