Generation and long-term persistence of new neurons in the adult zebrafish brain: a quantitative analysis.

Zebrafish, like other teleosts, are distinguished by their enormous potential to produce new neurons in many parts of the adult brain. By labeling S-phase cells with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU), quantitative analysis demonstrated that, on average, 6000 new cells were generated in the entire adult brain within any 30 min period. This corresponds to roughly 0.06% of the total number of brain cells. Part of these cells underwent a second round of cell division a few days after their generation so that 10 days post-BrdU administration, when the cells have exited the mitotic cycle, approximately 10,000 BrdU-labeled cells were present in the entire brain. At post-BrdU survival times of 446-656 days, on average 4600 BrdU-labeled cells were found, suggesting that approximately 46% of the cells present at 10 days persisted in the adult zebrafish brain. Combination of BrdU-labeling of mitotic cells with immunostaining against Hu showed that roughly 47% of the BrdU-labeled cells that persisted in the brain expressed this neuronal marker protein. Taken together, the results of this investigation demonstrate that at least half of the cells generated in the adult zebrafish brain develop into neurons and are likely to persist for the rest of the fish's life.