Neurogenesis, cell death and regeneration in the adult gymnotiform brain
Authors: Zupanc Günther K. H. 
Published: April 2021

Gymnotiform fish, like all teleosts examined thus far, are distinguished by their enormous potential for the production of new neurons in the adult brain. In Apteronotus leptorhynchus, on average 105 cells, corresponding to approximately 0.2 % of the total population of cells in the adult brain, are in S-phase within any period of 2 h. At least a portion of these newly generated cells survive for the rest of the fish’s life. This long-term survival, together with the persistent generation of new cells, leads to a continuous growth of the brain during adulthood.

Zones of high proliferative activity are typically located at or near the surface of the ventricular, paraventricular and cisternal systems. In the central posterior/ prepacemaker nucleus, for example, new cells are generated, at very high rates, in areas near the wall of the third ventricle. At least some of these cells differentiate into neurons, express immunoreactivity against the neuropeptide somatostatin and migrate into more lateral areas of this complex.

Approximately 75 % of all new brain cells are generated in the cerebellum. In the corpus cerebelli and the valvula cerebelli, they are produced in the molecular layers, whereas in the eminentia granularis the newborn cells stem from proliferation zones in the pars medialis. Within the first few days of their life, these cells migrate towards specific target areas, namely the associated granule cell layers. At least some of them develop into granule neurons.

The high proliferative activity is counterbalanced by apoptosis, a mechanism that resembles the processes known from embryonic development of the vertebrate brain. Apoptosis also appears to be used as an efficient mechanism for the removal of cells damaged through injury in the brain of adult Apteronotus leptorhynchus. Since apoptosis is not accompanied by the side effects known from necrosis, this ‘clean’ type of cell death may, together with the enormous proliferative activity in the brain, explain, at least partially, the tremendous capability of teleost fish to replace damaged neurons with newly generated ones.

One factor that appears to play a major role in the generation of new cells and in their further development is the neuropeptide somatostatin. In the caudal cerebellum of the gymnotiform brain, somatostatin-binding sites are expressed, at extremely high densities, at sites corresponding to the areas of origin, migration and differentiation of the newborn cells. This pattern of expression resembles the expression pattern in the rat cerebellum, where somatostatin immunoreactivity and somatostatin-binding sites are transiently expressed at the time when the granule cells of the cerebellum are generated. Moreover, after mechanical lesions of the corpus cerebelli, the expression of somatostatin-like immunoreactivity is tremendously increased in several cell types (presumably astrocytes, microglia and granule cell neurons) near the path of the lesion; the time course of this expression coincides with the temporal pattern underlying the recruitment of new cells incorporated at the site of the lesion.