title: Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice.
abstract: BACKGROUND
  In wild-type mice, axons of retinal ganglion cells establish topographically precise projection to the superior colliculus of the midbrain. This means that axons of neighboring retinal ganglion cells project to the proximal locations in the target. The precision of topographic projection is a result of combined effects of molecular labels, such as Eph receptors and ephrins, and correlated neural activity. In the Isl2/EphA3 mutant mice the expression levels of molecular labels are changed. As a result the topographic projection is rewired so that the neighborhood relationships between retinal cell axons are disrupted.
  
  
  RESULTS
  Here we study the computational model for retinocollicular connectivity formation that combines the effects of molecular labels and correlated neural activity. We argue that the effects of correlated activity presenting themselves in the form of Hebbian learning rules can facilitate the restoration of the topographic connectivity even when the molecular labels carry conflicting instructions. This occurs because the correlations in electric activity carry information about retinal cells' origin that is independent on molecular labels. We argue therefore that partial restoration of the topographic property of the retinocollicular projection observed in Isl2/EphA3 heterozygous knockin mice may be explained by the effects of correlated neural activity. We address the maps observed in Isl2/EphA3 knockin/EphA4 knockout mice in which the levels of retinal labels are uniformly reduced. These maps can be explained by either the saturation of EphA receptor mapping leading to the relative signaling model or by the reverse signaling conveyed by ephrin-As expressed by retinal axons.
  
  
  CONCLUSIONS
  According to our model, experiments in Isl2/EphA3 knock-in mice test the interactions between effects of molecular labels and correlated activity during the development of neural connectivity. Correlated activity can partially restore topographic order even when molecular labels carry conflicting information.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Tsigankov
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Koulakov
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods*; D003463:Cues; D055879:Gene Knock-In Techniques; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008959:Models, Neurological; D009415:Nerve Net / Q000196:embryology; D036121:Receptor, EphA3 / Q000235:genetics* / Q000378:metabolism; D036081:Receptors, Eph Family / Q000235:genetics*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D013477:Superior Colliculi / Q000166:cytology / Q000196:embryology*; D014157:Transcription Factors; D014795:Visual Pathways / Q000166:cytology / Q000196:embryology*
chemical_list: D018398:Homeodomain Proteins; C558561:Isl2 protein, mouse; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3; D036081:Receptors, Eph Family