Development of the motor system: Effects of radiation on developing corticospinal neurons and locomotor function

Abstract

Corticospinal (CS) neurons demonstrated by retrograde axonal HRP from the cord in adult rats were concentrated in a minor rostral band in area 10, projecting to the cervical cord, and a major caudal band, areas 3, 4, and 6, projecting as far as lumbar levels. The gap between the bands contained CS neurons projecting to the cervical cord only until age 2 weeks, but if the caudal band was ablated, the projections persisted. The problems investigated were (i) How would CS neurons develop postnatally and be distributed in rats prenatally irradiated on the 12th, 14th, 15th (150 R), or 17th day (150 or 200 R)? and (ii) Would answers to the foregoing help establish correlations between the development of structural and motor abnormalities? Most 12th-day-irradiated rats showed normal locomotion on difficult paths and nearly normally developing brain and cord structure, but rare CS neurons had bifurcated apical dendrites. Fourteenth and 15th-day rats had a thin cortex, a large subcortical ectopia, a malformed spinal cord, and a hopping gait. They showed diminished numbers of CS neurons in the cortex with persistent gap CS neurons, and CS neurons in the ectopia that mirrored those in the cortex. Hopping seemed to be generated in the cord, but supraspinal influences require further study. Seventeenth-day rats usually showed disordered locomotor rhythm and inability to adapt it to difficult paths, suggesting impairment of corticostriatal circuits. Some rats also showed inability to place limbs and feet during locomotion on difficult terrain, which resembled that following ablation of areas 3, 4, and 6. Dorsal cortex, including area 10, the chief source of corticostriatal projections in the rat, and areas 3, 4, and 6, was most severely malformed. Discrepancies between functional results of ablating area 10 and malforming it with radiation led us to suggest that abnormal thalamocortical and cortical wiring, for which there was evidence, as well as deficits, might be responsible for the abnormal locomotion.