| New neurons born in the ventricular zone of adult canaries are incorporated throughout the telencephalon, including the high vocal center (HVC), a nucleus involved in song acquisition and production. In adult males, neuronal recruitment in the HVC peaks at times of year when song is modified, and testosterone levels rise. This thesis addresses the following questions: (1) Do seasonal variations in testosterone levels regulate neuronal recruitment in the HVC? (2) What is the mechanism behind this regulation?; Initial experiments with adult female canaries revealed that testosterone did not affect the proliferation of ventricular zone cells. Instead, testosterone treatment increased the recruitment or survival of new neurons after they reached the HVC, both in females and castrated males. The total number of neurons in the HVC was not affected, suggesting that neuronal replacement might take place. The maintenance of high testosterone levels during the summer, when it is normally low, reduced recruitment in the fall, indicating that "vacancies" caused by the death of old neurons during the summer were necessary for neuronal replacement. This view was supported by the observation that castration doubled the number of pycnotic cells observed in the HVC.; A possible intermediary in the action of testosterone is brain derived neurotrophic factor (BDNF), a neurotrophin regulated by steroid hormones and neuronal activity. Both BDNF mRNA and protein were found in the HVC of adult males, as was its receptor, TrkB. BDNF infusion was found to have similar effects to testosterone, on neuronal recruitment in the HVC of females. Moreover, BDNF mRNA expression in the HVC of males varied seasonally, with singing, and with testosterone levels. BDNF protein in adult females, normally minimal, was also induced by testosterone treatment. Infusion of a neutralizing antibody to BDNF blocked neuronal recruitment in testosterone-treated females, indicating that BDNF is essential for this process.; On the basis of these experiments, a mechanism is proposed for the regulation of neuronal replacement in the HVC, whereby seasonal variations in testosterone levels regulate the production of BDNF, which in turn affects the death of old neurons and the survival of new ones in the HVC. |
