The role of EphrinA for the retinotopic map formation in mouse visual cortex

The mammalian cortex is arranged into a number of areas that represent our sensory, motor and cognitive functions. A characteristic feature of many sensory areas is their precise topographic organisation: in the same way as the “homunculus” in the somatosensory cortex represents the entire body surface, in the visual system retinal inputs are mapped topographically; i.e. spatial relationships in the visual field are maintained all the way to the primary visual cortex (area 17). The formation of such maps has been shown to depend on specific guidance molecules that are recognised by outgrowing axons. One major family of molecules implicated in axonal guidance and map formation are the ephrin ligands and their Eph receptors. These molecules have been shown to contribute to topographic mapping in several mammalian brain systems including the retinotectal and retinogeniculate projection. Much less is known about mechanisms that are important for the formation of topographic maps in the cortex. This study has investigated the role of ephrin-A ligands for the formation of the retinotopic map in the primary visual cortex of mice with optical imaging of intrinsic signals. Using grating stimuli presented at adjacent but non-overlapping positions within the visual field, I was able to visualise the retinotopic map in area 17 and resolve the pattern of retinotopic activity with high precision and reliability. In order to examine the influence of ephrinA ligands on cortical map formation, I used transgenic mice with a functional ephrin-A deficiency. These mice have a cDNA inserted into their genome that codes for a receptor antibody, which blocks all ephrin-As. I found an ordered retinotopic map in both wild type and transgenic mice, suggesting that other molecules or mechanisms apart from ephrin-A ligands are responsible for guiding thalamic axons to their target in the primary visual cortex. However, I also detected some important differences between the two genotypes: in ephrin-A knockout mice, the cortical representation of the peripheral visual field is compressed while that of the central field is expanded. Moreover, I applied the same paradigms to mice of about two weeks of age showing similar but evidently stronger effects in the young ephrin-A deficient mice, implying that initial errors in map formation can be corrected later in development. This observation suggests that the formation of topographic maps is not only regulated by genes that are expressed early in development, but that activity dependent neuronal plasticity plays a fundamental role, too.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Ludwig-Maximilians-Universität

Year

2003

Author dc:creator

• Creutzfeldt, Claire

Repository record source_url

https://edoc.ub.uni-muenchen.de/1689/

OAI identifier oai:identifier

oai:edoc.ub.uni-muenchen.de:1689