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Publication : Quantitative assessment of computational models for retinotopic map formation.

First Author  Hjorth JJ Year  2015
Journal  Dev Neurobiol Volume  75
Issue  6 Pages  641-66
PubMed ID  25367067 Mgi Jnum  J:242263
Mgi Id  MGI:5904738 Doi  10.1002/dneu.22241
Citation  Hjorth JJ, et al. (2015) Quantitative assessment of computational models for retinotopic map formation. Dev Neurobiol 75(6):641-66
abstractText  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.
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