This report covers the continuation of work which has in previous reporting periods been carried out within the Laboratory of Clinical Science, NIMH (Z01 MH 00798 LCS and Z01 MH 00799 LCS) and has now been consolidated into a single project. This work focuses on the normal development of the cerebral cortex in mice and rats using neuroanatomical techniques to study developing axonal connections. Our efforts have concentrated on the corticospinal and the callosal projections and have emphasized the role played by collateral elimination in the development of cortical connections. Experiments using anterograde tracers to examine the disposition of the corticospinal axons have shown that these attain a normal configuration in dysmylinated jimpy mutant mice. This argues against the notion that early myelin may determine the trajectory of the developing corticospinal projection. Experiments using retrograde tracers to label corticospinal neurons or callosally projecting neurons in jimpy mice have shown that the tangential distributions of these two projection systems undergo the normal developmental restriction in these mutant mice. This indicates that maturation of function accompanying myelination is not critical to the normally occurring developmental collateral elimination within these cortical projection systems. Experiments using heterotopic cortical transplants have identified position within the tangential plane of the cortex as a critical factor in determining which of the initially extended projections, cortical neurons maintain. Results of these and other studies provide support for the idea that similar cortical cell types are initially present throughout the tangential plane of the neocortex and that regional differences in mature cortical projection patterns may not be prespecified. However, our recent behavioral observations indicate that while homotopic cortical transplants can partially ameliorate some behavioral deficits that follow neonatal cortical lesions, heterotopic transplants do not, despite their seemingly appropriate projections. Thus, although position within the cortex influences the projections cortical neurons are able to maintain, early cortical neurons may indeed be, at least in some respects, prespecified as to their cortical region.
