Perinatal methylazoxymethanol acetate uncouples coincidence of orientation of cerebellar folia and parallel fibers

Abstract Perinatal administration of methylazoxymethanol acetate in the rat, as a one time injection on gestational day 21, postnatal days 0, 1 or 2, altered the parallel orientation of cerebellar folia. The effect persisted into adulthood. In animals injected on one of the postnatal days 3, 4 or 5, the folial pattern was not altered. Even when the injection was repeated for three days on postnatal days 3, 4 and 5, changes in the cerebellar surface were not found. However, in animals receiving a low protein diet during the last five days of gestation, the three injection regimen produced a distortion of the folial pattern. The surface of cerebella of animals injected on gestational day 21 through postnatal day 2 was covered with small blebs resembling the surface of a cauliflower head. In sagittal sections, islands of cortical laminae appeared to be isolated from the arbor vitae. However, serial reconstruction of the granular layer from sections revealed that these pieces were continuous with the arbor vitae. Surprisingly, cerebella having malaligned folia also had varying degrees of Purkinje cell somas distributed throughout the granule cell layer rather than in a single layer. This occurred even when the granule cell layer approached normal thickness. Analysis of cerebellar weight from the group injected on the day of birth revealed three levels of weight reduction: severe (>40%), moderate (20–40%) and mild ( In all animals treated with methylazoxymethanol acetate on days G21 through P5, parallel fibers were disoriented. This occurred even though the folia appeared normal in the G20, P3, P4, P5 and P3–5 injected groups. Bundles of parallel fibers crisscrossed in the plane of the cerebellar surface in all areas where a molecular layer was found. In sagittally sectioned regions of the vermis of moderately and mildly affected preparations, large bundles of parallel fibers traversed between folia in the sagittal plane. We conclude that factors controlling generation of parallel folia and those directing orientation of parallel fibers are not directly related to each other as might be predicted from their corresponding occurrence. Furthermore, the methylazoxymethanol acetate effect shows that the control over parallel aligned folia occurs over a three-day period extending from just before to 3 days after the time of birth.