Growth and target finding by axons of the corticospinal tract in prenatal and postnatal rats

Abstract The growth of the corticospinal tract was studied in prenatal and neonatal rats using the anterograde transport of horseradish peroxidase injected into the cerebral cortex as a marker in lightmicroscopic preparations. The findings were compared with electron-microscopic observations on normal material at the same ages. Labelled corticofugal axons traverse the diencephalon by gestational day 17.5, reach the pontine nuclei by gestational day 19.5, and the caudal limit of the medulla oblongata by gestational day 20.5, just before birth. On the day after birth, labelled corticospinal axons have crossed in the pyramidal decussation and extended into the dorsal columns of the upper cervical spinal cord. Corticospinal axons reach the thoracic segments by postnatal day 3, the lumbar segments by day 6 and the sacral segments by day 9. The lower end of the spinal cord is reached only after postnatal day 14. Beside the principal corticospinal tract in the dorsal columns, two other smaller corticospinal tracts occupy an intermediate position in the base of the cervical dorsal horn and a lateral position in the lateral white column. The intermediate tract is not found below cervical levels. Growth cones are seen at the tips of axons in light- and electron-microscopic material. The first corticospinal axons, less than 0.5 microns in diameter and grouped in tight fascicles, grow through a dense fabric of astrocytic and other glial processes in which no obvious pre-existing channels could be identified. Growth of corticospinal axons into the dorsal horn adjacent to the main tract is delayed until 2–3 days after the initial arrival of the tract at a given segment. This begins in the cervical segments only after the thalamocortical fibers have invaded the sensory-motor cortex though the parent pyramidal cells of the tract are still highly immature. The rate of extension of corticospinal axons is not constant. Growth down the dorsal columns is characterized by accelerated growth spurts on postnatal days 4 and 9. Much slower growth characterizes initial outgrowth through the diencephalon and later ingrowth into the spinal gray matter. There is approximately a three-fold increase in the numbers of corticospinal axons in the cervical segments between postnatal days 5 and 10. Myelination commences between postnatal days 10 and 12. It is concluded that the development of the corticospinal tract in the rat displays features that are common to other developing pathways in the rat and other species. Initial outgrowth of corticospinal axons is independent of afferent innervation, occurring at a time when the parent cell bodies are very immature. The early growth of corticospinal axons to the vicinity of their targets is followed by a substantial waiting period, comparable to that seen in other systems, before final invasion of the target. The factors responsible for the initiation of the second growth spurt, carrying axons into the target gray matter are not known. However, the final invasion of gray matter takes place only after the cells of origin of corticospinal axons have received a substantial afferent input. The rate of initial growth of corticospinal axons down the dorsal columns is not constant, but varies from region to region. Electronmicroscopy has failed to detect any morphological evidence for factors that might guide or promote the growth of corticospinal axons. The majority of corticospinal axons exclusive of the first ‘pathfinders’ seem to grow as tight fascicles in which individual axons contact only one another.