Figure 5.
Transplanted cells displace mossy fibers in the hilus but fail to suppress MFS in the inner molecular layer. Dual immunohistochemical staining for transplanted ESNP-derived neurons in RFP (red) and mossy fibers expressing ZnT-3 (green) was used to evaluate MFS in the hilus and iml of the dentate gyrus in TLE mice. A, MFS is not observed in the granule cell layer or iml in normal mice without prior seizure experience, B, TLE mice show moderate MFS by 6 weeks after SE after control stereotaxic injections of cell-culture medium devoid of ESNPs. C, More than 3 months after SE, much more extensive MFS in the iml is typical (five of eight TLE cases showed extensive MFS in iml). In the hilus, however, mossy fibers rarely overlapped with ESNP-derived neuronal arbors, and the mossy fiber projections were often displaced in the vicinity of the graft cores (n = 8). D, H, Typically, RFP+ axons from ESNP transplants invaded the iml and overlapped extensively with mossy fibers (n = 5 of 8). E–G, I–K, L, M–O, Only three of eight mice with transplants exhibited reduced MFS (L), despite extensive innervation of the iml by the transplanted neurons in all cases (E–G, I–K, M–O). hi, Hilus; gcl, granule cell layer. E–G, I–K, M–O are magnified views of boxed regions in D, H, and L, respectively. Arrowheads in E–G, I–K, M–O represent the outer limits of ZnT3 staining. Scale bars: A–C, 50 μm; D, H, L, 200 μm; E–G, I–K, M–O, 100 μm.