Fetal Neocortical Transplants Grafted into Neocortical Lesion Cavities Made in Newborn Rats: An Analysis of Transplant Integration with the Host Brain

Abstract

Fetal neocortical transplants placed into frontal cortex aspiration lesion cavities in newborn rats have been shown to survive and exchange connections with the host brain. To further study the afferent innervation of such transplants, enzyme- and immunohistochemical techniques were employed to examine the distribution of cholinergic, cat-echolaminergic and serotonergic fibers within the transplants, and radiochemical enzyme assays and high performance liquid chromatography were used to determine the content of neurotransmitter markers for these same fiber systems. To examine functional integration of the transplanted neurons in terms of activation of molecular signaling systems, the graft recipient animals were exposed to a novel open field environment. This behavioral testing paradigm is known to induce c-fos mRNA and Fos protein within several areas of the normal brain, including the sensorimotor cortex. Subsequent detection of the induction of this particular immediate early gene (transcription as well as translation) in the grafts would accordingly indicate genomic activation and therefore functional integration at the level of molecular signaling systems. Our results showed that these global fiber systems are distributed evenly throughout the extent of three mo old neocortical grafts and that the content of transmitter-related markers for these systems do not differ significantly from control cortex. Open field exposure of the grafted animals resulted in c-fos mRNA and Fos protein expression of cells distributed throughout the transplants. We conclude that the “global” fiber system innervation of neocortical transplants placed into newborn rats is similar to the innervation of normal cortex and that grafted neurons respond to host brain activation at the level of molecular signaling systems.