Critical stages for growth in the development of cortical neurons.

In order to study the role of efferent connectivity in the development of CNS neurons, the growth of pyramidal tract neurons within the hamster sensorimotor cortex was studied during normal development and after early postnatal lesions of the pyramidal tract. We first determined, by a combination of Nissl and retrograde HRP techniques, that within the lumbar representation of cortical layer 5B in adult animals two cell populations exist: a large-celled population (40% of the total) projecting to the spinal cord and a small-celled population (60% of the total) projecting intracortically and to targets rostral to the medulla. We could not determine whether large layer 5B cells in the infant sensorimotor cortex also represent the corticospinal population. Nevertheless, measurements of the growth in cross-sectional area of the large cells from 7 days postnatal to adulthood showed that these cells continue to grow until 51 days of age. The most rapid rate of growth occurs between 7 and 14 days, during which time the cross-sectional area of the cell bodies triples, coincident with the arrival of corticospinal axons in the lumbar cord and the beginning of target innervation (Reh and Kalil, '81). The growth of the large neurons in layer 5B was then charted after the pyramidal tract was cut ipsilaterally in the medulla at various postnatal ages. Early lesions of the tract (4-8 days postnatal) interrupt lumbar projection fibers before they establish synapses in the cord. Nevertheless, cortical cell bodies in the lumbar representation continue to grow normally after axotomy until 11 days after birth. At this time, large cells are arrested in development and their cell size remains in the 11-day stage (50% of normal adult large cell size) indefinitely. In contrast, adult lesions of the tract cause a 60% shrinkage of large cells, which in the adult represent corticospinal neurons. No evidence for cortical cell death was found after pyramidal tract lesions at any age. The results of axotomy reveal a turning point in the development of layer 5B cortical neurons. Before the age of 11 days the large cells have an independent program of cell growth that proceeds despite axotomy. After this time, the large cortical neurons appear to require intact axons for further growth and, in the absence of normal connectivity, are arrested in development.