Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared with mature neurons. However, there are conflicting reports on whether or not young neurons contribute to performance in behavioral tasks, and there is no clear relationship between the timing of maturation of young neurons and the duration of neurogenesis reduction in studies showing behavioral deficits. We asked whether these discrepancies could reflect differences in the properties of young neurons in mice and rats. We report that young neurons in adult rats show a mature neuronal marker profile and activity-induced immediate early gene expression 1-2 weeks earlier than those in mice. They are also twice as likely to escape cell death, and are 10 times more likely to be recruited into learning circuits. This comparison holds true in two different strains of mice, both of which show high rates of neurogenesis relative to other background strains. Differences in adult neurogenesis are not limited to the hippocampus, as the density of new neocortical neurons was 5 times greater in rats than in mice. Finally, in a test of function, we find that the contribution of young neurons to fear memory is much greater in rats than in mice. These results reveal substantial differences in new neuron plasticity and function between these two commonly studied rodent species.

In adult male zebra finches, high vocal center (HVC) neurons continuously die and are replaced. Many of these cells are projection neurons that form part of the efferent pathway controlling learned song production. Although it is known that HVC receives new neurons well into adulthood, it is unknown whether this occurs at a constant rate or declines with adult age. We used [3H]thymidine to label new HVC neurons in male zebra finches that were 3-36 months of age. Birds were killed 4 months after 3H injections to measure the long-term incorporation of new HVC neurons. HVC neurons projecting to the robust nucleus of the archistriatum (HVC-RA) were retrogradely labeled with Fluoro-Gold 4 d before death. We found a dramatic age-related decline in the number of 3H-labeled HVC-RA neurons present 4 months after cell birth dating. A similar decline in new HVC neurons was found as soon as 1 month after their formation. These results indicate that the production or early survival of adult-formed neurons decreases with age. HVC volume and total neuron number did not change with bird age, suggesting that the age-related decrease in new neuron addition was balanced by increased survivorship of neurons incorporated previously. Reliance of song structure on auditory feedback also wanes with age. We propose that with aging, fewer new cells are added as the numbers of functionally appropriate cells increase, a process that may be linked to age-related increases in motor program stability.

Neurogenesis and neuronal replacement in adulthood represent dramatic forms of plasticity that might serve as a substrate for behavioral flexibility. In songbirds, neurons are continually replaced in HVC (used as a proper name), a pre-motor region necessary for the production of learned vocalizations. There are large individual differences in HVC neuron addition. Some of this variation is probably due to individual differences in adult experience; however, it is also possible that heritability or experience early in development constrains the levels of adult neuron addition. As a step toward addressing the latter two possibilities, we explored the extent to which nest of origin predicts rates of HVC neuron addition in adult male zebra finches. One month after injections of [³H]-thymidine to mark dividing cells, neuron addition in HVC was found to co-vary among birds that had been nest mates, even when they were housed in different cages as adults. We also tested whether nest mate co-variation might be due to shared adult auditory experience by measuring neuron addition in nest mate pairs after one member was deafened. There were significant differences in neuron addition between hearing and deaf birds but nest mate relationships persisted. These results suggest that variation in genotype and/or early pre- or postnatal experience can account for a large fraction of adult variation in rates of neuron addition. These results also suggest that a major constraint on neurogenesis and the capacity to adjust rates of neuron addition in response to adult auditory experience is established early in development.