Adult Neurogenesis

The Discovery of Adult Mammalian Neurogenesis

Adult neurogenesis was an incidental discovery during the process of perfecting the complex 3H-thymidine autoradiographic technique. Adult-generated neurons were found sparsely scattered in the neocortex (Altman Science 1962.pdf). More studies in the 1960s showed extensive adult neurogenesis in the hippocampus, and in the 1980s Shirley Bayer showed that the new neurons in the dentate granular layer actually added to the adult population in rats.  In the 1990s adult neurogenesis was “rediscovered,” and those studies often did not give credit to the original Altman – Bayer work. Adult-generated neurons are routinely found in the granular layer of the dentate gyrus in the hippocampus and in the granular layer the olfactory bulb (see the olfactory development page). Here are our studies on the adult-generated hippocampal dentate granule cells; the new literature on hippocampal adult neurogenesis has expanded on what we presented many years ago.

Altman Anat Rec 1963.pdf
The arrow indicates a labeled hippocampal granule cell in a young adult rat that was injected two times intraperitoneally with 3H-thymidine at 4 months (one week interval between injections) and survived to 5 months (counterstained autoradiogram). This is Figure 13 in the above paper and is the first illustration (among others in the paper) of a hippocampal neuron generated during the adult period.

INFORMATION ADDED OCTOBER, 2014:  A brief communication from our laboratory documents the histological evidence for a subgranular zone in the dentate gyrus of children aged 1 month to 6 years.  This finding supports the hypothesis that the dentate granular layer in humans has the same developmental pattern as in other mammals.


Neurons in the Rat Dentate Gyrus Granular Layer Substantially Increase During Juvenile and Adult Life

Bayer et al Science 1982.pdf

These data are volumetric granule cell nuclei throughout the entire hippocampus in rats ages 30, 120, 200, and 365 days. The important finding is thzt the granule cell population substantially increases its numbers with age. The adult-generated neurons are adding to the population.

Changes in the Total Number of Dentate Granule Cells in Juvenile and Adult Rats A Correlated Volumetric and 3H·Thymidine Autoradiographic Study*

Bayer-Exp Br Res 1982. pdf

These figures show that the dispersed germinal matrix in the adult dentate gyrus is a fragmentary scattering of small, dark cells in the dentate hilus (*, Fig. 3) called the subgranular zone (Altman and Bayer, 1975, see below).

Initially, 3H-thymadine is picked up by precursor cells in the subgranular zone during the S-phase of the cell cycle.  Some progeny become neurons that differentiate into mature granule cells. The graph in figure 4 shows that when animals survive longer after injections, there is a higher proportion of labeled mature granule cells(black bars) compared to immature cells (clear bars). See also fig. 5 in Altman&Das JCN 1965.pdf

Figure 2 in Altman&Bayer hippo dev 1975.pdf shows the heavy 3H-thymidine label uptake by presumptive granule cell precursors in the dispersed subgranular zone in the hilus (HI) of the dentate gyrus. As rats mature, the subgranular zone is scattered small cells at the junction between the base of the granule cell layer and the hilus (Fig. 3 center). Many of the postnatally-generated and all of the adult-generated dentate granule cells arise in the subgranular zone. (AH, Ammon’s horn; GL, dentate granular layer; MO, dentate molecular layer)