FETAL NEOCORTICAL TRANSPLANTS GRAFTED INTO NEOCORTICAL LESION CAVITIES MADE IN NEWBORN RATS - AN ANALYSIS OF TRANSPLANT INTEGRATION WITH THE HOST BRAIN

Fetal neocortical transplants placed into frontal cortex aspiration le sion cavities in newborn rats have been shown to survive and exchange connections with the host brain. To further study the afferent innerva tion of such transplants, enzyme- and immunohistochemical techniques w ere employed to examine the distribution of cholinergic, catecholamine rgic 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 fibe r systems. To examine functional integration of the transplanted neuro ns in terms of activation of molecular signaling systems, the graft re cipient animals were exposed to a novel open field environment. This b ehavioral testing paradigm is known to induce c-fos mRNA and Fos prote in within several areas of the normal brain, including the sensorimoto r cortex. Subsequent detection of the induction of this particular imm ediate early gene (transcription as well as translation) in the grafts would accordingly indicate genomic activation and therefore functiona l integration at the level of molecular signaling systems. Our results showed that these global fiber systems are distributed evenly through out the extent of three mo old neocortical grafts and that the content of transmitter-related markers for these systems do not differ signif icantly from control cortex. Open field exposure of the grafted animal s resulted in c-fos mRNA and Fos protein expression of cells distribut ed throughout the transplants. We conclude that the ''global'' fiber s ystem innervation of neocortical transplants placed into newborn rats is similar to the innervation of normal cortex and that grafted neuron s respond to host brain activation at the level of molecular signaling systems.