Cells that took up tritiated thymidine (H-3T) at various periods of intrauterine and early infant life in the periventricdar proliferative zone and migrated to form the isocortex in the rat were tracked autoradiographically in series of stages to characterize their movements. Cells labeled at any stage soon separated themselves into cohorts, some continuing to proliferate, others migrating a t once, and still others delaying before migrating. Migratory cells moved to the developing cortex along the curved and oblique paths of the pallial fibers, whose basic plan was established by the early thalamocortical fibers. Magnitude of speed was 15 to 30 I.L per hour. The primitive neural cells that originated on each of the fourteenth to eighteenth intrauterine days first reached the cortex in about 48 hours, others took two or three days longer. Migrations originating on the nineteenth to twenty-first days continued into the week after birth; as the primitive cells approached the cortex, however, they differentiated into young neurons, and traveled perpendicularly to its outer part. The first cohort of twentieth day labeled cells reached their intracortical destinations in about three days, the last in about ten days. The isocortex was formed essentially from within outward. The first neuroglia destined for the isocortex arose on the twenty-first intrauterine day.

Normal and abnormal development of movement in the rat were studied by investigating the growth and organization of the motor-sensory cortexcorticospinal tract system (MSC-CST) and the functional and morphologic effects of ablating the MSC or quadrants of it at different ages. Major growth of the MSC outflow, the CST, in the brain stem and rostral cord occurred in the second and third weeks postnatally, coinciding approximately with the normal mid-week transition from infantile to mature locomotion. Ablation of the MSC at birth revealed that while the MSC-CST was not essential for ordinary locomotion on flat terrain, its presence hastened normal development of this kind of movement, and that it was absolutely essential for locomotion on difficult terrain. The MSC quadrants showed quite different, and in some domains mutually exclusive, CST projection patterns to forebrain, diencephalon, brain stem, and spinal destinations (determined by Fink-Heimer-Nauta fiber degeneration studies). Ablation of some quadrants produced distinctive syndromes of disordered movement: the posterolateral quadrant related to active grasping in positioning limbs, while the posteromedial quadrant related to tactile motor-sensory positioning of limbs. Thus in addition to the classic somatotopic organization of the MSC, there was another kind of organization into regions concerned with components of integrated movement of a number of parts of the body. Several forms of aberrant circuitry developed after MSC ablations in infants, but their possible roles in functional adaptation remain to be determined.

Immature mammals are widely believed to compensate functionally for nervous system alterations better than adults with comparable disorders. Embryos restitute huge losses, but plasticity, remodeling, or use of alternate mechanisms said to underly compensation in injured infants are not understood. Toward understanding these, the effects of ablating or altering parts of the nervous system in infant and mature rats are being studied. In these experiments one lateral half of the forebrain and diencephalon was largely removed at birth or maturity and the consequences to nervous system structure and motor-sensory and visual behavior were observed. Similarities between animals operated on as adults or infants were loss of tactile placing opposite the ablation, ability to discriminate visual patterns, and gauge variable jumping distances visually. Some subjects performed the visual tasks using the eye opposite the hemispherectomy alone, which was exclusively supplied with uncrossed retinogeniculate fibers. Differences were: loss of tactile placing after operation in infants was delayed until the seventeenth day; stride was impaired in animals operated on as adults but was spared in infant subjects ; with appropriate ablations, Fink-Heimer-Nauta stains showed that after hemispherectomy, infants, but not adults, developed a small, uncrossed corticospinal tract. The stride component in locomotion seemed dependent on the corticospinal tract system, and was partially dissociated from the placing reaction essential for locomotion on rough terrain. The possibility was considered that the small remodeled corticospinal tract spared the stride component.

No abstract

FIFTEEN FIGURRSPrevious studies (Hicks, '54a, ?58, Hicks, Brown. and D 'Amato, '57) have described the mechanisms of the malf ormations following 150-200 r in the earlier stages of development and have provided some data on effects of higher and lower doses. The present study describes the rnalformative patterns that result when rats are irradiated with 150-200 r on one of the days of gestation, 12 to 20, and sorrie of the mechanisms involved in their formation. Eft'ects on the retina and cerebellum will he briefly considered, but because these structures continue to he radiosensitive and subject to malformation well into neonatal life, they will be the subjects of further separate studies.