In contrast to mammals, fish exhibit an enormous potential to produce new cells in the adult brain. By labeling mitotically dividing cells with 5-bromo-2'-deoxyuridine (BrdU), we have characterized the development of these cells in the zebrafish (Danio rerio). Proliferation zones were located in specific regions of the olfactory bulb, dorsal telencephalon (including a region presumably homologous to the mammalian hippocampus), preoptic area, dorsal zone of the periventricular hypothalamus, optic tectum, torus longitudinalis, vagal lobe, parenchyma near the rhombencephalic ventricle, and in a region of the medulla oblongata lateral to the vagal motor nucleus, as well as in all three subdivisions of the cerebellum, the valvula cerebelli, the corpus cerebelli, and the lobus caudalis cerebelli. In the valvula cerebelli and the corpus cerebelli, the young cells migrated from their site of origin in the molecular layers to the corresponding granule cell layers. By contrast, in the lobus caudalis cerebelli and optic tectum, no indication of a migration of the newly generated cells over wider distances could be obtained. BrdU-labeled cells remained present in the brain over at least 292 days post-BrdU administration, indicating a long-term survival of a significant portion of the newly generated cells. The combination of BrdU immunohistochemistry with immunolabeling against the neural marker protein Hu, or with retrograde tracing, suggested a neuronal differentiation in a large portion of the young cells.

Whereas in mammals postnatal neurogenesis, gliogenesis, and angiogenesis appear to be kept at low rates, in fish the capability for the production of new brain cells during adulthood is very pronounced. Many of the newly generated cells originate from germinal layers that maintain their proliferative activity during adulthood. By employing incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU) into mitotic active cells, we have quantitatively mapped such proliferation zones in the brain of adult Apteronotus leptorhynchus (Gymnotiformes, Teleostei). In the telencephalon, diencephalon, mesencephalon, and rhombencephalon, the total number of BrdU-labelled cells was low, making up approximately 25% of all mitotic active cells in the brain. Many of these cells were scattered over wide areas. Otherwise, zones of high proliferative activity were typically located at or near the surface of ventricular, paraventricular, and cisternal systems. Approximately 75% of all BrdU-labelled cells found in the brain of adult Apteronotus leptorhynchus were situated in the cerebellum. Zones displaying proliferative activity were restricted to small areas, such as narrow stripes around the midline of corpus cerebelli and valvula cerebelli, the boundary between corpus and valvula, and a large portion of the area covered by the eminentia granularis medialis. Counts indicate that, on average, 100,000 cells, corresponding to approximately 0.2% of the total population of cells in the brain of adult Apteronotus leptorhynchus, are in S-phase within a period of 2 hours. At least part of these newly generated cells is added to the population of already existing cells. This leads to a permanent growth of the brain with increasing size of the fish, a process that appears to slow down only in individuals of relatively advanced age.

Fish are distinctive in their enormous potential to continuously produce new neurons in the adult brain, whereas in mammals adult neurogenesis is restricted to the olfactory bulb and the hippocampus. In fish new neurons are not only generated in structures homologous to those two regions, but also in dozens of other brain areas. In some regions of the fish brain, such as the optic tectum, the new cells remain near the proliferation zones in the course of their further development. In others, as in most subdivisions of the cerebellum, they migrate, often guided by radial glial fibers, to specific target areas. Approximately 50% of the young cells undergo apoptotic cell death, whereas the others survive for the rest of the fish's life. A large number of the surviving cells differentiate into neurons. Two key factors enabling highly efficient brain repair in fish after injuries involve the elimination of damaged cells by apoptosis (instead of necrosis, the dominant type of cell death in mammals) and the replacement of cells lost to injury by newly generated ones. Proteome analysis has suggested well over 100 proteins, including two dozen identified ones, to be involved in the individual steps of this phenomenon of neuronal regeneration.