This work focuses on the normal development of the cerebral cortex using neuroanatomical techniques to study developing axonal connections in mice and rats. We have concentrated on the corticospinal projections and the role played by collateral elimination in the development of cortical connections. Experiments using homotopic and heterotopic transplants of rat cerebral cortex during development have identified position within the tangential plane of the host cortex as a critical factor in determining which of the initially extended projections cortical neurons will maintain. However, our observations on forelimb placing behaviors in such preparations suggest that some early specification of cortical regional locale may occur. The results to date are most consistent with a progressive specification of cortical regional fate. Experiments using anterograde axonal tracers to label corticospinal axons have revealed the time course and distribution of an aberrant ipsilateral corticospinal projection in rats with unilateral damage to the rostral cortex. These studies indicate that this aberrant projection may arise through the maintenance and elaboration of a small ipsilateral component of the corticospinal projection which is normally present only transiently during development. Experiments in WLD mice using anterograde tracers, histochemical and histophysical methods indicate that post-lesion axonal sprouting in the hippocampus is delayed in this mutant and that the extent of the delay of sprouting differs among projection systems. This is consistent with the notion that axonal degeneration is pivotal to the initiation of axonal sprouting and also suggests that different axonal systems may respond differentially to sprouting cues.
