In humans and other animals, gonadal secretions influence sexual differentiation of brain function and behavior. The research proposed in this application aims to elucidate the neural mechanism underlying this differentiation. The focus will be on the vasopressin projections of the sexually dimorphic bed nucleus of the stria terminalis, and the medial amygdaloid nucleus. A prime advantage of studying a particular neurotransmitter system is that one can better estimate whether process involved in sexual differentiation indiscriminately affect developing cells in sexually dimorphic areas, or whether they target specific cells. Furthermore, since one can easier trace connections of cell groups for which the neurotransmitter is known, one can identify brain areas that may be affected by the sexual differentiation of the system under study. Vasopressin projections are a particular case in point. They are very attractive to study, since they are extremely sexually dimorphic: males have many more vasopressin-immunoreactive cells and fibers than females have. Moreover, the effects of hormonal manipulations on these projections are so dramatic, that they can be analyzed reliably. By hormonally manipulating these pathways during development, this research tries to analyze whether and, if so, when gonadal steroids influence the sexual differentiation of the vasopressin pathways. It also tries to reveal which properties of vasopressin projections are sexually differentiated by focusing on the capacity of individual cells to synthesize AVP, on the total number of cells that can synthesize vasopressin, and on the density of the projections. Finally, this research tries to study whether the target tissue influences the differentiation of vasopressin pathways by transplanting neural tissue that contain steroid-sensitive vasopressin neurons into vasopressin-deficient Brattleboro rats. In conclusion, this research will help to identify mechanisms that contribute to sexual differentiation of neurotransmitter systems, and hence to sexual differentiation of brain function and behavior.
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