Autoradiographic and histological studies of postnatal neurogenesis. III. Dating the time of production and onset of differentiation of cerebellar microneurons in rats

Abstract

In one experiment rats were injected with single does of thymidine‐H 3 at 6 hours, 2, 6 and 13 days of age, or with multiple doses during two periods of early life, and were killed when 2, 4 and 6 months old. In the autoradiographic analysis attention was focused on the time of origin and differentiation of basket, stellate and granule cells in different regions of the cerebellar cortex. In another, non‐radioactive study, in rats ranging in age from newborn to adult, the development of the cerebellum was studied with quantitative and qualitative histological techniques. In the sagittal plane the area of the cerebellum increases over 20‐fold from birth to 21 days. This increase is primarily due to the growth of the cerebellar cortex, much of the increment in the area of the subcortical regions occurring after 21 days. During the first week the growth of the different layers, excepting the proliferative external granular layer, is sluggish. During this period, the cells of the external granular layer do not differentiate but provide stem cells to this growing proliferative matrix. These proliferating and migrating cells of the external granular layer are the precursors of the basket, stellate and granule cells of the cortex; glia cells probably arise from cells multiplying locally. The first cells to differentiate are situated in the lower half of the molecular layer and include basket cells. Stellate cells differentiate later, with a peak at the end of the second week. The bulk of granule cells differentiate during the second and third weeks, with 25–80% of them, depending on the region, being formed between 11–21 days. These differences, together with several histological criteria (thickness of external granular and molecular layers, appearance of Purkinje cells) were used for constructing regional developmental maps of the cerebellar cortex. Granule cells differentiate in the depth of vermian fissures before they do over the exposed surfaces of the lobes; the ventral lobes (lingula and nodulus) mature before the anterior lobes; and the last maturing vermian lobes are the tuber, declive and culmen. The hemispheres, with some exceptions, mature later than the vermis, with the paraflocculus being among the last maturing structures.