Developmental factors related to abnormal cerebellar foliation induced by methylazoxymethanol acetate (MAM).

Quantitation of mid-sagittal sections of the molecular layer, and both the external and internal granular layers between control and methylazoxymethanol acetate (MAM)-treated rats, at various stages of cerebellar development revealed a much smaller area of these layers in sagittal profile, however, the fiber core was not significantly affected by the drug. The expansion of the pial surface length was parallel to the length of the Purkinje cell layer, although comparison of a fissure index revealed hypofissuration in the experimental group. In histological examination, there was perforation, patching, and agenesis of the external granular layer. Mushroom expansion of the external granular layer occurred at patches producing a gyrating folial pattern rather than parallel ones. The number of lobules and their basic pattern remained normal. We conclude that the deficits in the external granular layer interrupted the growth force that produces the normal rostrocaudal organization of parallel coronal foliation and this resulted in shallow periodic fissuration along the sagittal extent. Fissurations forming lobules arose largely independent of the external granular layer by directed expansion of the central fiber core while normal parallel foliation is an elaboration of the lobular surface controlled by growth forces defined by both distribution of the external granular layer and the underlying fiber core with associated Purkinje cells.