Efferent Projections to the Host Brain from Intrastriatal Striatal Mouse-to-rat Grafts: Time Course and Tissue-type...

The developmental time-course and growth characteristics of efferent graft-to-host projections were studied from mouse fetal striatal grafts (E13 - 14) implanted as a cell suspension into the ibotenate-lesioned striatum of immunosuppressed adult rats. A cell surface monoclonal antibody specific for mouse neurons (M6) was used to identify the donor cells and their projections into the host brain. At 3 - 5 days after implantation, sparse fascicles of M6-positive graft-derived fibres extended for approximately 0.3 - 0.4 mm across the graft - host border into the surrounding host striatum. From the beginning they were selectively orientated in one direction, i.e. caudally along the myelinated fibre bundles of the internal capsule. At 8 days, the graft-derived fibres were more numerous and more densely labelled. They ran in dense fascicles inside the myelinated bundles of the host internal capsule and reached the rostral host globus pallidus, a distance of approximately 1.2 mm from the caudal tip of the graft. Two weeks after grafting, the M6-positive fibre fascicles were clearly seen to branch within the globus pallidus to form terminal-like networks. From this time onwards, the immunoreactivity of the outgrowing fibre fascicles gradually diminished, although small but dense terminal-like networks could be found in the host globus pallidus in most, but not all, of the rats at longer survival times (3 - 15 weeks). This is consistent with previous work showing that outgrowing axons lose their M6 immunoreactivity as they mature and become myelinated. Control grafts of fetal neocortical and fetal cerebellar tissue were used to assess the tissue-type specificity of the efferent fibre growth. The neocortical implants projected densely up to about 3 mm into the host brain, along the internal capsule and the corpus callosum and into the overlying cortex. By contrast, although the cerebellar grafts survived well, they showed very little efferent fibre growth. Double immunostaining for DARPP-32 and M6 revealed that all M6-positive fibre fascicles extending from the striatal (but not neocortical) grafts also showed DARPP-32 positivity, and thus that it was the DARPP-32-positive regions of the striatal grafts that projected to the host brain. It is concluded that graft-to-host projections, running along and inside host myelinated bundles, are formed from intrastriatal striatal grafts within 1 - 2 weeks of implantation. Grafts of neocortical tissue grew well along the same trajectory, whereas neurons of a type not normally projecting along the internal capsule, i.e. cerebellum, failed to extend axons over any significant distance along this trajectory.