A Hypothesis About the Functional Role of Neurogenesis in the Adult Hippocampus

throughout evolution; it has been observed in the central nervous systems of invertebrates and vertebrates such as fish, birds, and mammals (1, 5, 10, 26). Most studies carried out under physiological conditions in adult mammals indicate that significant levels of neurogenesis occur exclusively in the dentate gyrus of the hippocampus (DG; FIGURE 1) and the olfactory bulb (OB). In the adult human brain, neurogenesis has been detected in the DG (9), but no evidence of adult-born neurons has yet been found in the OB (35). Newly generated neurons derive from multipotent neural progenitor cells (NPCs) that proliferate, migrate, and differentiate into specific neuronal phenotypes (10). It is very striking that, whereas NPCs are highly ubiquitous in the adult brain, neurogenesis remains very much restricted to the subgranular zone (SGZ) of the DG and the subventricular zone of the lateral ventricles (SVZ). The SGZ and SVZ give rise primarily to dentate granule cells (DGCs; FIGURE 1) and interneurons of the OB, respectively (1, 10). Growing evidence indicates that new neurons become functionally integrated in the existing circuits (2, 4, 16, 39, 52), although the true physiological relevance of adult neurogenesis remains unknown. The spatial restriction observed in adult neurogenesis suggests that most regions of the adult brain may not require new neurons for their normal function. Therefore, at least two possibilities emerge: 1) that the adult brain shuts off neurogenesis and what is left during adulthood is a remnant of development without physiological significance; or 2) that neurogenesis is required for a very specific set of brain functions that are concentrated primarily in the hippocampus and OB. If the latter were true, those specific functions are yet to be discovered. Increasing evidence suggests that neurogenesis may play a key role in olfactory processing in the adult brain (6, 11, 33, 40). A thorough review of this topic has been recently published (18), and therefore this review will focus on the putative functional role of newly generated neurons in the adult mammalian hippocampus. We will discuss current data in the context of a plausible hypothesis that describes how new neurons could modify hippocampal function. The proposed hypothesis exploits the notion that adult neurogenesis might serve as a powerful mechanism for plasticity of brain circuits.