title: Quantitative assessment of computational models for retinotopic map formation.
abstract: Molecular and activity-based cues acting together are thought to guide retinal axons to their terminal sites in vertebrate optic tectum or superior colliculus (SC) to form an ordered map of connections. The details of mechanisms involved, and the degree to which they might interact, are still not well understood. We have developed a framework within which existing computational models can be assessed in an unbiased and quantitative manner against a set of experimental data curated from the mouse retinocollicular system. Our framework facilitates comparison between models, testing new models against known phenotypes and simulating new phenotypes in existing models. We have used this framework to assess four representative models that combine Eph/ephrin gradients and/or activity-based mechanisms and competition. Two of the models were updated from their original form to fit into our framework. The models were tested against five different phenotypes: wild type, Isl2-EphA3(ki/ki), Isl2-EphA3(ki/+), ephrin-A2,A3,A5 triple knock-out (TKO), and Math5(-/-) (Atoh7). Two models successfully reproduced the extent of the Math5(-/-) anteromedial projection, but only one of those could account for the collapse point in Isl2-EphA3(ki/+). The models needed a weak anteroposterior gradient in the SC to reproduce the residual order in the ephrin-A2,A3,A5 TKO phenotype, suggesting either an incomplete knock-out or the presence of another guidance molecule. Our article demonstrates the importance of testing retinotopic models against as full a range of phenotypes as possible, and we have made available MATLAB software, we wrote to facilitate this process.
authors.affiliation: Cambridge Computational Biology Institute, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, CB3 0WA, United Kingdom.
authors.forename: J J Johannes
authors.initials: JJ
authors.lastname: Hjorth
authors.affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, EH8 9AB, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Sterratt
authors.affiliation: Cambridge Computational Biology Institute, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, CB3 0WA, United Kingdom.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Cutts
authors.affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, EH8 9AB, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Willshaw
authors.affiliation: Cambridge Computational Biology Institute, Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, CB3 0WA, United Kingdom.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Eglen
mesh_terms: D000818:Animals; D001931:Brain Mapping; D036342:Ephrins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D051379:Mice; D008822:Mice, Transgenic; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D012160:Retina; D013477:Superior Colliculi / Q000502:physiology; D014793:Visual Cortex / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology*
chemical_list: D036342:Ephrins; D009419:Nerve Tissue Proteins
keywords: computational modelling framework; mouse; quantitative evaluation; retinocollicular projection; retinotopic map formation