Purkinje cell dendritic alterations after transient developmental injury of theexternal granular layer

Abstract

To examine the influence of granule cell axons on morphogenesis of their major synaptic target, the Purkinje cell dendrites, a transient injury of the external granular layer of developing rat cerebellum was induced by injecting 10 mg/kg methylazoxymethanol acetate on postnatal days 1, 2, 3 and 4. The antiproliferative action of the drug resulted in a diminution of the mitotic population which slowed the expansion of the internal granular and molecular layers. This was followed by a reconstitution of a thicker than normal external granular layer and a late phase of extensive growth. Perturbations of Purkinje cell dendritic morphology induced by this altered timing of granule cell accumulation were studied with Golgi-Cox impregnation techniques. Systematic observation were made of a number of defined abnormalities of Purkinje cells which included somas positioned below the normal monolayer; elongated dendrites; multiple somatic dendrites; S-shaped dendrites; dendrites disoriented away from the radial direction; and portions of dendrites below the soma of origin. The results indicated that most of these 'abnormalities' occur to a small extent in normal cerebellum but that these experimental conditions induced a bias in favor of their appearance. Some dendritic abnormalities, i.e., dendrites tilted out of the sagittal plane, dendrites directed toward the white matter, and apical dendrites growing vertically between cells of the external granular layer, were not noted in normal cerebellum and we attribute these particular changes to unique developmental possibilities occuring only after a more or less severe injury. This analysis of bias in dendritic morphology subsequent to subtle developmental injury provides informat on on processes of normal development and on the genesis of phylogenetic variants of Purkinje cell morphology.