J.R. Newton*, J. Sharma, H. Yu, M. Sur
Picower Center for Learning & Memory, Department of Brain & Cognitive Sciences, MIT, Cambridge, MA, USA

The Eph receptor tyrosine kinases and their ephrin ligands have distinct complementary gradients in the thalamus and cortex. Ephrins are known to play an important role in topographic mapping; however their role in establishing the organization and patterning of cortical areas is unknown. We have examined the size, location and eye-specific driving of visual cortex in adult normal and ephrin A2/A5 knock-out mice using optical imaging of intrinsic signals. Visual field elevation and azimuth were mapped by monocularly presenting a single high-contrast bar drifting in periodic fashion. Images were analyzed by extracting the Fourier component of the intrinsic signal at the periodicity of the drifting bar. We find that although their size remains similar, the location of V1 and V2 in ephrin A2/A5 knock-out mice is shifted significantly medial and anterior relative to their location in normal mice. There is also an expansion of the ipsilateral representation within V1 and V2 of the knock-out mice. The shift in the location of V1 and V2 is consistent with a cortical ephrin A5 gradient (Bolz et al., 2004). The expansion of the ipsilateral representation is consistent with expanded retinogeniculate projections in ephrin A2/A5 knock-out mice (Ellsworth et al., 2004), which is due to removal of an ephrin gradient in the LGN (Feldheim et al., 1998). Thus, the organization of visual cortex reflects two distinct roles of ephrins: a cortical gradient that influences location and regionalization of V1 and V2, and a thalamic gradient that influences eye-specific patterning within these areas.

Support: NIH grants EY13900 (JRN), EY11512 and NS39022 (MS).