Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice

Tsigankov, D., Koulakov, A. A. (2010) Sperry versus Hebb: topographic mapping in Isl2/EphA3 mutant mice. BMC Neurosci, 11. p. 155. ISSN 1471-2202 (Electronic) 1471-2202 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/21190559
DOI: 10.1186/1471-2202-11-155

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. CONCLUSION: 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.

Item Type: Paper
Uncontrolled Keywords: Animals Body Patterning/ physiology Brain Mapping/ methods Cues Gene Knock-In Techniques Homeodomain Proteins/ genetics/metabolism Mice Mice, Knockout Mice, Mutant Strains Models, Neurological Nerve Net/embryology Receptor, EphA3/ genetics/metabolism Receptors, Eph Family/ genetics Retina/cytology/ embryology Retinal Ganglion Cells/cytology/metabolism Superior Colliculi/cytology/ embryology Visual Pathways/cytology/ embryology
Subjects: organs, tissues, organelles, cell types and functions > organs types and functions > brain
bioinformatics > computational biology
organism description > animal > mammal > rodent > mouse
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Koulakov lab
Depositing User: CSHL Librarian
Date Deposited: 19 Oct 2011 18:21
Last Modified: 18 Jan 2017 17:51
PMCID: PMC3019204
URI: http://repository.cshl.edu/id/eprint/15572

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