To date, the amount of conclusive evidence linking adult neurogenesis and learning is small (). This limited understanding can be partially attributed to the fact that appropriate methods to manipulate and monitor new neuron production in adulthood do not exist. Thus, a critical direction for future research examining the role of adult-generated neurons in learning will be the development of new techniques such as transgenic mice in which new neuron production in the DG could be selectively and reversibly ablated. Beyond this, more refined molecular techniques could be used to detect changes in the new cells as the animal is engaged in a learning experience.
Evidence in Favor of and Against a Role for Adult Neurogenesis in the Hippocampus in Learning and Memory
Even with these new technologies, a number of fundamental questions will remain. For example, what are the mechanisms by which cell production in the DG is regulated during learning? Do new neurons rescued by learning show different patterns of connectivity relative to other adult-generated neurons or those generated during development? Is gene expression in new neurons affected by learning and does it differ from that in mature neurons? At an information processing level, how does a new population of neurons interact with those neurons that were generated during development and how do these interactions lead to the formation of new memories without destroying old memories? Addressing most of these questions will require a better understanding of the functional maturation of adult-generated neurons (Carlen et al., 2002
; Dayer et al., 2003
; Ambrogini et al., 2004b
) as well as insight into the differences and similarities between neurons generated during development vs. those produced in adulthood. Until now, addressing such issues has been inhibited by technical limitations but may be more feasible given a number of recent advances. It is now possible to use dual cell cycle labels with markers of cell phenotype (Vega and Peterson, 2005
). This method could allow for not only the comparison of developmentally and adult-generated neurons in the same animal, but also how these different cell populations are affected by learning. Addressing differences in gene expression in adult-born neurons can be achieved with laser capture microdissection (LCM). LCM has recently been used to demonstrate differential gene expression in replaceable vs. nonreplaceable populations of neurons in birds and mice (Lombardino et al., 2005
). Combining LCM with immunocytochemistry could then be used to show how learning alters gene expression within the new neuron itself.
Clearly, a definitive link between adult neurogenesis in the hippocampus and learning remains to be established. Whether or not a role for adult-generated neurons in learning and memory is ultimately ruled out, alternative functions should be considered. One possibility is that adult neurogenesis is a vestige of development, which, in adulthood, has no functional significance. However, given the substantial number of new neurons that are produced in the hippocampus in adulthood (Cameron and McKay, 2001
; Dayer et al., 2003
), even in humans (Eriksson et al., 1998
), it is unlikely that these cells serve no function. Alternatively, new neurons may contribute to other functions of the hippocampus, such as anxiety and stress regulation, or they may serve as a latent mechanism for endogenous repair of this brain region, known for its susceptibility to ischemia and seizures. Now that a critical mass of neuroscientists are turning their attention to the questions of adult neurogenesis with open minds, definitive answers will undoubtedly emerge.