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.