Evidence that late-generated granule cells do not simply replace earlier formed neurons in the rat dentate gyrus

Summary

Ten-day-old Sprague-Dawley rats were injected intraperitoneally with ³H-thymidine (³HTdR) and allowed to survive until postnatal day (P) 40, P120, P200, P300 or P450. Following the preparation of the tissue for autoradiography, the location of the labeled neurons within the granule cell layer of the dentate gyrus was determined at two different septo-temporal levels. At P40 the labeled cells in the suprapyramidal blade of the dentate gyrus were found only in the deep part of the granule cell layer, where it borders on the hilus, and more than four cell diameters from the molecular layer. The latter relationship remained constant at each of the five ages studied, but between P40 and P120 the average distance from the labeled granule cells to the hilus almost doubled. At the middle of the temporal portion of the dentate gyrus this trend continues with age, so that by P450 the labeled neurons, though no nearer to the molecular layer than at earlier stages, were found, on average, in the middle of the granule cell layer, more-or-less halfway between the hilus and the molecular layer. Near the middle of the septal half of the dentate gyrus a similar pattern was seen at P40 and P120 but thereafter the labeled cells within the granule cell layer remained at about the same distance from the hilus. These observations permit the following three conclusions: (i) there is a gradual accumulation of dentate granule cells throughout the life of Sprague-Dawley rats; (ii) the newly-generated cells are preferentially added to the deep aspect of the granule cell layer from which they progressively displace the earlier-formed cells; and (iii) there is no concomitant loss of a corresponding number of earlier-generated granule cells: in other words, there is no substantial “turnover” of granule cells in adult animals.