Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography.

Neurogenesis in the rat hippocampal region was examined with 3H-thymidine autoradiography. The rats in the prenatal groups were the offspring of pregnant females given two injections of 3H-thymidine on consecutive days in an overlapping series: embryonic (E) day E13+E14, E14+E15,…, E21+E22. The rats in the postnatal (P) groups were injected in two nonoverlapping series: first, the day of birth (PO) and P1, P2+P3,…, P18+P19; second, P0–P3, P4–P7,…, P16–P19. On 60 days of age, the percentage of labelled cells and the proportion of cells added during each day of formation were determined at several anatomical levels within each structure of the hippocampal region (entorhinal cortex, parasubiculum, presubiculum, subiculum, Ammon's horn, and the dentate gyrus) and the hippocampal rudiment (tenia tecta, indusium griseum). The neurons in each structure arise in overlapping, but still significantly different, waves: the hippocampal rudiment between E16–E17; the entorhinal cortex between E15–E17; the para- and presubiculum between E16–E19; the subiculum between E16–E18; large cells in strata oriens, radiatum, lacunosum-moleculare of Ammon's horn between E15–E17; Ammon's horn pyramidal cells between E17–E19; large cells in the dentate hilus and molecular layer between E15–E19. Dentate granule cells begin to originate on E17, and 10% of the population forms after P18. There are three characteristic gradients of formation within structures. First, deep cells are generated before superficial cells. Second, cells closer to the rhinal fissure are formed before those lying farther away (“rhinal to dentate” gradient). Third, later forming cells are flanked by earlier forming superficial and deep cells (“sandwich gradient”) in the entorhinal cortex (layer III cells originate after layers II and IV), Ammon's horn (pyramidal cells originate after large cells in strata oriens, radiatum, and lacunosum-moleculare), and the dentate gyrus (granule cells originate after large cells in the hilus and molecular layer). There is a “rhinal to dentate” gradient between structures. The entorhinal cortex starts first, next is the subiculum, then field CA3 of Ammon's horn, and finally, the dentate gyrus. Two structures are exceptions to this gradient. The para- and presubiculum form significantly later than the subiculum, and CA1 forms significantly later than adjacent CA3 cells; this late neurogenesis may be related to prominent thalamic input to both structures. Neurogenetic gradients between the cells providing laminated afferent input to the Ammonic pyramidal and dentate granule cells correlate with their order of termination: afferents from progressively later-originating cells terminate progressively closer to the cell body. Topographic hippocampal projections along the dorsoventral axis correlate with formation patterns in target structures: dorsal hippocampal fibers project to zones occupied by earlier-forming cells in the lateral septal nucleus and pars posterior of the mammillary body; ventral hippocampal fibers project to zones occupied by later-forming cells in these structures.