Neurogenesis in the Adult Olfactory Bulb

Abstract

For over a century, a central paradigm in the field of neuroscience has been that the capacity of germinal layers to generate neurons was restricted to the embryonic period, and that new neurons are not added to the adult mammalian brain (Ramon y Cajal 1913). Occasional early reports of neurogenesis in the adult central nervous system (CNS) (Allen 1912; Levi 1898) were ignored, probably because of the impossibility to determine with certainty the neuronal nature of the cells presenting mitotic figures. In more recent times, the pioneering work of Altman (1962), followed by the studies of Kaplan and Hinds (1977), have reproposed, this time with more compelling evidences, that new neurons are added in discrete regions of the adult brain, the olfactory bulb (OB) and the dentate gyrus (DG) of the hippocampus (for a historical review, see Kaplan 2001). These reports were initially ignored, then followed by negative reactions and critical publications that did not confirm the existence of newborn neurons in adults (for a review of the controversy, see Gross 2000). After the finding that in reptiles new neurons continue to be added to most of the telencephalon throughout life (for a review, see Garcia-Verdugo et al. 2002), the paradigm shift leading to the acceptance of the notion of adult neurogenesis in higher vertebrates has known an important acceleration thanks to the discovery of neurogenesis in birds, related to the appearance of seasonal song (for review, see Nottebohm 1989). Nevertheless, these initial discoveries confronted the persistent assumption that adult neurons did not undergo proliferation, the last trench being dug at the level of the mammalian brain (Rakic 1985). The turning point of the collective perception about neurogenesis occurred with the demonstration that adult mammalian brain neurons are also capable of mitosis, and that newborn neurons can migrate and integrate into existing circuitries (for review, see Gross 2000). Interestingly, this particular new form of structural brain plasticity is specific to discrete brain regions and most investigations concern the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampus (for a review, see Lledo et al. 2006). Although, in the past, occasional reports have appeared suggesting neurogenesis also at the cortical level (Gould et al. 1999), an elegant paper appeared a few years ago (Bhardwaj et al. 2006) providing almost definite proof that, contrary to other cell types in the brain parenchyma, no new cortical neurons are generated after the perinatal period. Taking advantage of the integration of C-14 generated by nuclear bomb tests and by analyzing neocortical tissue of patients who received bromodeoxyuridine (BrdU), the study provides compelling evidence that there is no biologically significant neocortical neurogenesis in adult humans.