Neocortical Grafting To Newborn And Adult Rats: Developmental, Anatomical And Functional Aspects (advances In Anatomy, Embryology And Cell Biology)

This report presents the results of neural transplantation experiments that were designed either to study neural developmental phenomena or to appraise the possible restorative capacity of grafts. The first part of the report deals with the findings of transplantation studies that were performed in newborn recipient rats in an attempt to determine the importance of extrinsic or intrinsic factors in the process of areal cortical differentiation. More precisely, we examined the extent to which extrinsic signals drive the pattern of efferent connections of neurons residing in different cortical areas. In the first experiment, we examined the general distribution pattern of efferents arising from homotopic as compared to heterotopic transplants of embryonic cortical tissue placed into the frontal cortex of newborn rats. Our findings indicated that embryonic occipital neurons transplanted heterotopically into the sensorimotor cortex: (a) only rarely contacted normal targets of the motor cortex, (b) systematically projected towards normal targets of the visual cortex, and (c) distributed fibers to structures normally receiving fibers from both the motor and visual cortex, either exclusively into the visual corticorecipient zone of the structure or into both the visual and motor corticorecipient zones. In the second experiment, we attempted to assess the densities of the spinal projections arising from homotopic or heterotopic transplants implanted into the frontal or occipital cortex of newborn rats. We provided evidence that transplants of embryonic neocortical neurons of frontal origin developed and maintained a spinal cord projection whatever their rostrocaudal position within the host neocortex, whereas transplants of occipital origin did not maintain a significant spinal cord projection in adulthood. Finally, in the third experiment, we analyzed the laminar and tangential distribution of the tectal projections developed by transplants of embryonic occipital cortex placed into the primary or secondary subdivisions of the occipital cortex of newborn rats. Abnormalities in the laminar and/or tangential organization of the tectal distribution of the transplant efferents were systematically found. Using these different transplantation paradigms, we provided increasing evidence that, in their heterotopic location, the embryonic neurons retain some of the developmental characteristics corresponding to their embryonic cortical site of origin. Our findings strongly suggested, therefore, that there is an early specification of neocortical neurons to develop area-specific efferents. In conclusion, converging lines of evidence suggest that regional differences in the neuroepithelium are predetermined early in development, thus leading to cerebral cortex parcellation, as hypothesized by Rakic (1988). In the second part of the report, we describe the results of a series of experiments dealing with the consequences of grafting embryonic cortex into the damaged cortex of adult rats. These effects were examined from an anatomical, metabolic, behavioral, and electrophysiological point of views. The experiments were conducted using either the frontal or the visual cortex as models to appraise the functional integration of the grafts into the motor or visual circuits, respectively. The first study was undertaken to examine the capacity of transplants of embryonic frontal neocortical tissue placed into the frontal cortex of an adult recipient to develop efferents into the host CNS. The results indicated that transplants of fetal neocortex placed into adult CNS had the capacity to develop efferents which seemed to grow over significant distances within the host corpus callosum but, in most cases, failed to penetrate deeply into the gray matter. The density of the efferent projections was, however, far weaker than that seen in newborn hosts. In the second study, the 2-deoxyglucose (2-DG) technique was used to examine the functional integration of hom The first experiments with neural transplantation into the brain (for a review, see Bjorklund and Stenevi 1985) were reported at the end of the last century by Thompson (1890), who took cortical tissue from adult cats and implanted the tissue pieces into the neocortex of adult dogs. The neurons did not survive, but the transplanted mass did not disintegrate entirely. Successful graft­ ing into the brain was reported later by Ranson (1909), who implanted spinal ganglia into the cerebral cortex of developing rats, and by Dunn (1917), who reported survival of implanted neonatal cortex into the cortex of newborn recipients. Another important step was made by Le Gros Clark (1940) who reported that, in the rabbit, embryonic (E) cortical tissue could be successfully grafted into the cortex of young recipients. Ex­ periments by Wallace and Das (1982), and Bjorklund and Stenevi (1984), showing behavioral effects of grafts, subsequently stimu­ lated a growing interest in neurotransplantation research. Intrac­ erebral grafting is now considered a powerful tool for addressing fundamental questions about development, regenerative, or re­ storative phenomena in the central nervous system (CNS) and is a potential therapy for neurodegenerative diseases. The mechanisms that govern the development of the neural circuitry are still largely unknown. Actually, it is not clearly established to what extent areal cortical differentiation depends on environmental or genetic factors. The first part of the present report deals with the findings of several transplantation studies, performed in newborn recipient rats, in which these developmental issues were addressed. In humans, the cerebral cortex can be affected by a variety of diseases and, therefore, several experimental studies have been undertaken to determine to what extent transplantation of cortical neurons could be proved as a useful treatment for cerebral cortical damage. The second part deals with the functional effects of transplantations performed in adult recipient rats. Front Matter....Pages I-XI Transplantation of Embryonic Cortex into Newborn Host Cortex: A Means to Study Neural Development....Pages 1-32 Transplantation of Embryonic Cortex into the Damaged Cortex of Adult Rats....Pages 33-70 Summary....Pages 71-72 References....Pages 73-84 Back Matter....Pages 85-86