Genesis and death of vocal control neurons during sexual differentiation in the zebra finch.

Several song-related regions in the adult zebra finch brain have substantially more neurons in males than in females. Such differences appear to arise from sex differences in circulating steroids during early posthatch life. In the present study, developmental mechanisms involved in the production of sex differences are explored by examinations of the normal time course of posthatch neurogenesis and cell death in vocal control circuits. As a first step toward determining whether rates of neuron production may be different in males and females, tritiated thymidine, a marker of cell division, was administered to zebra finches at various times during the first month after hatching. Birds were sacrificed at 60 d. The number of cells formed after hatching and present at 60 d was then evaluated in 3 vocal control regions--HVc (hyperstriatum ventralis pars caudalis) and its 2 principal targets, RA (robust nucleus of the archistriatum) and Area X. Cell death was quantified by counts of normal and pyknotic, degenerating cells made in these nuclei in additional, untreated birds of both sexes at 5 d intervals from 5 to 45 d of age. The combined results of these experiments suggest that differential cell death is a major factor in the development of sex differences in the song control system and provide the first direct evidence for sex differences in cell death in the developing telencephalon. Although developmental time tables differ among the 3 brain areas examined, at specific ages significantly higher numbers of pyknotic cells were observed in HVc, RA, and presumptive Area X in females compared to males. Peak levels of cell death in RA occur 4-6 weeks after hatching. This is about 3 weeks after the onset of sex differences in steroid levels that, in turn, lead to differential organization of song system nuclei. This pattern of results suggests that designation for death and actual cell loss are temporally dissociated in this system. Neuron proliferation for HVc and Area X, but not RA, continues throughout the first 30 d after hatching, and a significant sex difference was found in the number of cells present in HVc at 60 d that were formed after hatching. Comparisons of the timing of cell death and cell incorporation suggest that this difference may be best accounted for by differential survival of neurons formed after hatching rather than differential rates of neuron production. Neither differential neurogenesis nor differential neuron death can fully account for the apparent extreme sexual dimorphism in the number of neurons in Area X.(ABSTRACT TRUNCATED AT 400 WORDS)