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.

The vertebrate optokinetic nystagmus (OKN) is a compensatory oculomotor behavior that is evoked by movement of the visual environment. It functions to stabilize visual images on the retina. The OKN can be experimentally evoked by rotating a drum fitted with stripes around the animal and has been studied extensively in many vertebrate species, including teleosts. This simple behavior has earlier been used to screen for mutations affecting visual system development in the vertebrate model organism zebrafish. In such a screen, we have found a significant number of homozygous belladonna (bel) mutant larvae to be defective in the correct execution of the OKN [1]. We now show that about 40% of homozygous bel larvae display a curious reversal of the OKN upon visual stimulation. Monocular stimulation leads to primary activation of ipsilateral eye movements in larvae that behave like the wild type. In contrast, affected larvae display contralateral activation of eye movements upon monocular stimulation. Anatomical analysis of retinal ganglion cell axon projections reveal a morphological basis for the observed behavioral defect. All animals with OKN reversal are achiasmatic. Further behavioral examination of affected larvae show that OKN-reversed animals execute this behavior in a stimulus-velocity-independent manner. Our data support a parsimonious model of optokinetic reversal by the opening of a controlling feedback loop at the level of the optic chiasm that is solely responsible for the observed behavioral abnormality in mutant belladonna larvae.

In contrast to adult mammals, adult teleost fish regularly generate new neurons and glial cells in many brain regions. A previous quantitative mapping of the proliferation zones in the brain of adult Apteronotus leptorhynchus (Teleostei, Gymnotiformes) has shown that 75% of all mitotically active cells are situated in the cerebellum (Zupanc and Horschke [1995] J. Comp. Neurol. 353:213-233). By employing the thymidine analogue 5-bromo-2'-deoxyuridine, we have, in the present study, investigated the postembryonic development of this brain region in detail. In the corpus cerebelli and the valvula cerebelli, the vast majority of newborn cells originate in the respective molecular layers. Within the first few days of their life, these cells migrate toward specific target areas, namely, the respective granule cell layers. In the caudal part of the cerebellum, the granule cell layer of the eminentia granularis pars medialis displays the highest mitotic activity. From there, the cells migrate through the adjacent molecular layer to the granule cell layer of the eminentia granularis pars posterior. Combination of retrograde-tracing techniques with immunohistochemistry for 5-bromo-2'-deoxyuridine showed that at least a portion of the newly generated cells develop into granule neurons. Many of the newly generated cells survive for long periods of time. A large fraction of these cells is added to the population of already existing cells, thus resulting in a permanent growth of the target areas and their associated structures.