Noninvasive bioluminescence imaging of c-fos expression in the mouse barrel cortex

Expression of immediate early genes, such as c-fos, has been extensively used as a marker of neural activity. However, their expression in the brain has so far been examined by using invasive procedures. In this study, we tried to image c-fos expression in the mouse barrel cortex noninvasively by detecting bioluminescence produced by the reporter luciferase. To detect asymmetry in c-fos expression in the bilateral barrel cortices, we used ten Fos-Luc mice and removed long whiskers on one side. After 1h of exploration in a novel cage, luciferin was intraperitoneally administrated under gas anesthesia and bioluminescence was measured with a cooled CCD camera. We observed moderate but clear emission over the head that was significantly stronger on the side of removal. After regrowth of the whiskers, the same mice had the vibrissae clipped on the other side. Bioluminescence was again dominant on the side of removal. In three of the mice, c-fos expression was examined immunohistochemically. The distribution of bioluminescence generally agreed with that of the c-fos positive cells though the bioluminescence tended to distribute wider, by around 0.5mm, probably due to scattering of light through the tissues. The results show that expression of c-fos in the mouse barrel cortex can be imaged repeatedly and noninvasively in the living animal.