Cholinergic innervation of fetal neocortical transplants is increased after neutralization of myelin-associated neurite growth inhibitors.

Fetal neocortical transplants placed into adult neocortical sensorimotor aspiration lesions are known to receive afferent input from the adult host rat brain. As this input is less dense than normal, the present study was designed to investigate whether neutralization of myelin-associated neurite growth inhibitors NI-35/250 might promote host derived cholinergic innervation of fetal neocortical transplants. Adult rats received unilateral sensorimotor cortical aspiration lesions, and block grafts from embryonic day 14-15 neocortical tissue were placed immediately into the lesion cavities. Mouse hybridoma cells secreting either the monoclonal antibody IN-1, which blocks neurite growth inhibitors NI-35/250, or a control antibody or medium without cells were applied in millipore filter capsules directly over the fetal graft tissue. The brains were processed 12 weeks later for the visualization of acetylcholinesterase-positive, presumptive cholinergic fibers. We found an enhancement in the cholinergic innervation of fetal grafts in the recipients treated with the antibody IN-1 both in terms of fibers growing into the graft and of density within the center of the grafts. These results indicate that myelin-associated neurite growth inhibitors are involved in the development of host-transplant connectivity in the adult brain.