Michael Kaplan (biologist) - Research Background

Research Background

Initial studies that suggested that the adult brain could generate new neurons were largely ignored. In the 1960s Joseph Altman and coworkers published a series of papers reporting that some dividing cells in the adult brain survived and differentiated into cells with morphology similar to neurons. They used tritiated thymidine autoradiography to label the cells. Tritiated thymidine is incorporated into the DNA of dividing cells. They found that the highest density of labeling was in the subventricular zone and in the dentate gyrus of the hippocampus. It was known that the dentate gyrus of the hippocampus is essentially devoid of glia. Therefore, Altman attributed the labeling in this region to the uptake of thymidine by dentate granule cells. However, he could not prove that the adult-generated cells were neurons rather than glia, since no phenotypic markers were available that could be used in conjunction with thymidine autoradiography. The absence of specific markers for neurons and glia and continued skepticism surrounding the novel concept of adult neurogenesis limited further development of the research.

In the mid 1970s and the early 1980s, Michael Kaplan and his colleagues reexamined the initial observations using the electron microscope and added substantial confidence that neurogenesis could occur in the adult brain. Combining electron microscopy and tritiated thymidine labeling, they showed that labeled cells in the rat dentate gyrus have ultrastructural characteristics of neurons, such as dendrites and synapses. Although they were able to demonstrate this in repeatable studies in primate cortex, most researchers at the time did not consider this to be evidence of significant neurogenesis in adult mammals.

In addition, the concept that there may be brain stem cells that could proliferate, migrate, and then differentiate into new neurons had not yet been introduced. It was therefore thought that mature neurons would have to replicate, an idea that most researchers found incredible. Furthermore, the possible relevance of the findings for humans was underestimated because there was no evidence of neurogenesis in primates.