This work focuses on the normal development of the cerebral cortex and its connections utilizing neuroanatomical techniques in mice and rats. Much of our effort has concentrated on the pyramidal tract through which the corticospinal axons pass on their way from the cortex to the spinal cord. We have also studied the development of the basal forebrain cholinergic projections to the cortex. Experiments involving heterotopic cortical transplants have allowed us to identify position within the tangential plane of the cortex as a critical factor in determining which of the initially extended projections, a cortical neuron will maintain. Results of these and other experiments, including our observations utilizing an antibody to a soluble brain protein, support the notion that certain neocortical cell types are present throughout the tangential plane of the neocortex. However our recent behavioral observations suggest that while homotopic cortical transplants may help ameliorate behavioral deficits following neonatal cortical lesions, heterotopic transplants do not, despite their seemingly appropriate projections. Experiments utilizing dysmylineated jimpy mutant mice have shown that myelin does not play a critical role in determining the trajectory of developing corticospinal projection. Observations utilizing retrogradely transported fluorescent dyes and the carbocyanine dye Dil, have shown that the basal forebrain projection to the cortex develops progressively, at no time displaying errors as do many other developing axonal systems. There are however distinct patterns which characterize the development of the innervation of the various targets of the cholinergic basal forebrain.
