Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging

The molecular mechanisms that coordinate the functional organization of the mammalian neocortex are largely unknown. We tested the involvement of a pu tative guidance label, ephrin-A5, in the functional organization of the som atosensory cortex by quantifying the functional representations of individu al whiskers in vivo in adult ephrin-A5 knock-out mice, using intrinsic sign al optical imaging. In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development. In adult ephrin-A5 knock-ou t mice, we found a spatial gradient of change in the amount of cortical ter ritory shared by individual whisker functional representations across the s omatosensory cortex, as well as a gradient of change in the distance betwee n the functional representations. Both gradients of change were in correspo ndence with the developmental expression gradient of ephrin-A5 in wild-type mice. These changes involved malformations of the cortical spacing of the thalamocortical components, without concurrent malformations of the intraco rtical components of individual whisker functional representations. Overall , these results suggest that a developmental guidance label, such as ephrin -A5, is involved in establishing certain spatial relationships of the funct ional organization of the adult neocortex, and they underscore the advantag e of investigating gene manipulation using in vivo functional imaging.