The cytogenesis and morphogenesis of the rat hippocampus was examined with the techniques of 3H-thymidine autoradiography, cell pyknosis produced by low-level X-irradiation, and quantitative histology.

The procedure of progressively delayed cumulative labelling was used for autoradiography. Groups of rats were injected with four successive daily doses of 3H-thymidine during non-overlapping periods ranging from birth to day 19. They were killed at 60 days of age, and the percentage of labelled cells was determined. The pyramidal cells of Ammon's horn and the polymorph cells of the dentate gyrus are not labelled postnatally, confirming earlier conclusions of their prenatal origin. In the dentate gyrus, 85% of the granule cells are formed postnatally, with 45% forming during the first week. The majority of the small cells of the dentate molecular layer and of the Ammonic strata oriens, radiatum, and lacunosum-moleculare are formed during the second week.

As an aid to locating the proliferative compartments of the hippocampus during development and to characterize the time course of both cell differentiation and morphological development, rats ranging in age from gestation day 17 to postnatal day 103 were killed six hours after one exposure to 200r X-rays, and the pyknotic cells were counted. Cell pyknosis in Ammon's horn reaches a maximal level prenatally and declines rapidly during the early postnatal period. Cell pyknosis in the dentate gyrus reaches its highest level during the second postnatal week and declines gradually with some radiosensitive cells still present in the adult. Immature granule cells are also at their highest level during the second postnatal week, while mature granule cells gradually accumulate to attain asymptotic levels at around two months of age. The alignment of the pyramidal cells to form the characteristic curvature of Ammon's horn occurs shortly after pyramidal cell cytogenesis is completed. Conversely, the sharp fold in the dentate gyrus is apparent from the day of birth onward, before the completion of granule cell cytogenesis. Possible mechanisms for the morphological development of the dentate gyrus along with a consideration of the possible migratory route of granule cell precursors is also discussed.