Fetal tectal transplants in the cortex of adult rats become innervated both by retinal ganglion cell axons regenerating through peripheral nerve grafts and by cortical neurons

Abstract

The present work elucidates the connectivity of adult retinal ganglion cell axons regenerating through grafted peripheral nerve segments with co-grafted immature brain target cells. The optic nerve of rats was transected intraorbitally and its segment distal to the transection was replaced by a 3 cm length of peroneus communis graft, that is known to permit regeneration of a certain proportion of the severed axonal population. Five weeks after optic nerve transection and peripheral nerve transplantation the regenerating optic tract axons were guided into rat fetal mesencephalic co-grafts (E14-16) placed in superficial cavities prepared in the occipital cortex. The rationale of the experimental setup was based on the fact that regrowth of retinal axons started at the 6th day after transection, whereas the fastest-growing axons reached the distal end of the transplanted peripheral nerve 4 weeks later growing with a velocity of about 1.33 mm/day. Therefore, grafting the fetal superior colliculus at the time axons arrive distally resulted in ingrowth of several hundreds of retinal axons into this immature, retinoreceptive brain tissue. Retinal axons which penetrated the fetal grafts contacted tectal neurons and GFAP-immunoreactive glia and formed typical retinocollicular axonal arbors as detected by anterograde labeling with RITC from the retina. In addition, sprouting fibers from the adjacent adult cortical neurons penetrated frequently the fetal transplants. By 'bridging' lesions with peripheral nerve pieces and providing immature neurons as targets for growing neurites, this transplantation model is suitable for investigations on whether regenerating adult neurites are capable of reforming connections. The co-transplantation technique may serve as a tool for understanding whether interrupted circuitries in the central nervous system can be functionally restored over long distances by the use of peripheral nerve grafts and immature nervous system tissue.