Maturational sequence of newly generated neurons in the dentate gyrus of the young adult rhesus monkey.

The generation of new neurons in the hippocampal dentate gyrus of adult mammals has been characterized in rodents, but the details of this process have not been described in the primate. Eleven young adult rhesus monkeys were given an injection of the DNA synthesis phase marker bromodeoxyuridine (BrdU) and killed at varying survival intervals (2 hours to 98 days). The immature neuronal marker TUC-4 (TOAD/Ulip/CRMP-4) was used to define three stages of morphological maturation. Stage I neurons had small somata and lacked dendrites. Stage II neurons had larger somata and short dendrites. Stage III neurons were similar in size to mature granule cells and had branching dendrites that extended into the molecular layer. Examination of TUC-4-positive immature neurons colabeled with BrdU indicated that stage I neurons first appeared 2 days after BrdU injection, stage II neurons at 14 days, and stage III neurons at 35 days. Electron microscopy of TUC-4-labeled cells showed that stage I cells had ultrastructural features of immature neurons, whereas stage III neurons were similar to mature granule cells and formed synapses in the molecular layer. This suggests that stage III neurons could potentially integrate into the circuitry of the dentate gyrus. This study shows that the maturational sequence for new neurons in the adult monkey is similar to that of the adult rodent; however, maturation takes a minimum of 5 weeks in the monkey, which is substantially longer than what has been reported in rodents.