NEURAL SUBSTRATES FOR REPRODUCTIVE BEHAVIOR

这项研究的目的是了解细胞和 控制性分化的分子机制 大脑。特别是，我们正在调查男性特有的 性腺雄激素的分泌模式调节 细胞的增殖、存活、突触连接和功能 以肌肉和运动神经元为目标。 我们利用了一种高度的性别二态系统-- 控制发声的神经元和肌肉 确定功能性性行为发展中的关键事件 不同之处。我们现在的具体目标是进一步了解 雄激素分泌在细胞内控制性分化 水平和一组分子--雄激素受体，GAP 连接蛋白、肌球蛋白亚型--参与这一过程 个体发育过程。我们将研究一下 喉部使用的性二型肌纤维类型 组织化学和免疫细胞化学。肌球蛋白亚型将 被生化分离；我们将确定何时典型的性行为 首先，表达方式出现了分歧。我们将研究分子基础 成人肌纤维染料偶联的个体发育史 女性。我们计划检查乙酰胆碱的性别差异 喉部突触终末的释放和数量 神经肌肉接头。中国社会性别差异的根源 喉运动神经元数量与性二型性中枢神经系统 将探索互联互通。我们将测量雄激素水平 和受体在性腺后的大脑中的表达 差异化。使用内分泌应用和消融， 激素对关键细胞和分子作用的临界期 将建立流程。直接投资的相对贡献率 对肌肉和神经靶点的作用与间接、突触作用 调解后，将对行动进行评估。 发育过程中雄激素的分泌控制着大脑的性别 大多数脊椎动物的分化。内分泌紊乱 功能或在雄激素受体蛋白中与 临床功能障碍包括假两性畸形、睾丸 女性化、神经内分泌异常和改变 性别认同。了解受以下因素影响的基本流程 神经和肌肉中的类固醇激素可以通过研究得出 在动物模型中，并将提供对潜在的 人类疾病的细胞和分子机制。

The aim of this research is an understanding of the cellular and molecular mechanisms that govern the sexual differentiation of the brain. In particular, we are investigating how male-specific patterns of secretion of gonadal androgens regulate the proliferation, survival, synaptic connectivity and function of target muscle and motor neurons. We have exploited a highly sexually dimorphic system--the neurons and muscles that control vocalizations in X. laevis--to identify key events in the development of functional sex differences. Our specific aims now are to further understand how androgen secretion controls sexual differentiation at the cellular level and how a set of molecules--the androgen receptor, gap junction proteins, myosin isoforms-- participate in this ontogenetic process. We will examine the development of sexually dimorphic muscle fiber types in larynx using histochemistry and immunocytochemistry. Myosin isoforms will be separated biochemically; we will determine when sex typical expression first diverges. We will investigate the molecular basis and ontogenetic history of dye coupling of muscle fibers in adult females. We plan to examine sex differences in acetylcholine release and number of synaptic terminals at the laryngeal neuromuscular junction. The origins of sex differences in laryngeal motor neuron number and sexually dimorphic CNS connectivity will be explored. We will measure androgen levels and receptor expression in brain just after the gonads differentiate. Using endocrine application and ablation, the critical periods for hormone action on key cellular and molecular processes will be established. The relative contributions of direct action on muscle and nerve targets versus indirect, synaptically mediated, actions will be assessed. Androgen secretion during development controls brain sexual differentiation in most vertebrates. Disorders in endocrine function or in androgen receptor proteins are associated with clinical dysfunction including pseudohermaphroditism, testicular feminization, neuroendocrine abnormalities and alterations in gender identity. An understanding of basic processes affected by steroid hormones in nerve and muscle can be derived from study in animal models and will provide useful insights into underlying cellular and molecular mechanisms of human disorders.