HOMOTOPIC, BUT NOT HETEROTOPIC, FETAL CORTICAL TRANSPLANTS CAN RESULTIN FUNCTIONAL SPARING FOLLOWING NEONATAL DAMAGE TO THE FRONTAL-CORTEXIN RATS

Experiments involving the heterotopic transplantation of neocortex dur ing development have indicated that the efferent connections maintaine d by the transplant as well as other organizational features are appro priate to the transplant's regional locale within the host cortex, rat her than to its site of origin within the donor cortex, These findings would seem to be consistent with the idea that developing cortical ne urons lack any rigid regional specification. To examine this further, we made lesions in the rostral cortex of newborn rats and placed piece s of either rostral or occipital fetal cortex into the lesion site. Ad ditional cases with similar lesions, but with no transplants, were als o prepared, When the animals matured, behavioral testing was done to i dentify any residual deficits. Compared with lesioned animals that had received no transplants, animals with homotopic transplants show a su bstantial sparing in certain forelimb placing and somatosensory tasks. In marked contrast, animals with heterotopic transplants did not show any sparing. Indeed, when placing reactions were elicited by vibrissa l stimulation (vibrissae --> forelimb placing; extinction-placing) the animals with heterotopic transplants showed a greater impairment than the lesioned animals that received no transplants. These results indi cate that while homotopic fetal cortical transplants may help ameliora te behavioral deficits that normally follow neonatal lesions of the ro stral cortex, heterotopic transplants do not, and may in fact exacerba te the deficits, despite the fact that such heterotopic transplants ha ve been shown to maintain projections that seemingly are appropriate t o their locale, These findings indicate that at a stage when fetal cor tical neurons retain the potential to extend axons to targets appropri ate for a variety of cortical regions, their capacity for complete fun ctional integration into heterotopic cortical regions may already be r estricted. This may imply that a progressive determination of regional cortical attributes occurs during normal fetal development.