NEURAL SUBSTRATES FOR REPRODUCTIVE BEHAVIOR

这项研究的目标是了解荷尔蒙如何， 尤其是类固醇--雄激素和雌激素，控制性 特定发育的靶神经元和肌肉产生成熟 男性或女性的表型。这些问题是理解 男性和女性典型的临床疾病。激素导向细胞 发展是前列腺癌和乳腺癌的基础，疾病 二次性分化，如雄激素不敏感和 假性失语症与性别确立的至少某些方面 身份。这项建议的重点是控制细胞类型在 喉肌纤维和喉部神经肌肉交界处 非洲爪哇。这种实验准备提供了一个很好的模型 一种研究次生生物细胞和分子基础的系统 性别分化。发声器官或喉咙的发育是 由于内分泌的性别差异而导致的高度性别二型性 周围的环境。孤立的喉头可以发出实际的发声， 识别男性和女性特有的电生理学和 不同的发声曲目背后的肌肉特征 成年雄性和雌性。这些差异包括性别差异 突触效能-男性弱突触与男性强突触 女性--在肌肉纤维类型--男性和男性的纤维迅速收缩 女性的纤维慢慢收缩。突触强度和突触强度的控制 本课程将检验突触随使用而提高效力的能力。 在男性和女性喉部使用电生理和染料成像 方法：研究方法。钙离子进入突触前终末后 使用钙敏感的荧光染料；性行为的潜在机制 差异-包括离子通道和其他方面的性别差异 将研究变送器释放的各个方面。发展中的 本课程将探讨突触效能性别差异的根源。 初步结果有力地表明，突触的性别差异 体力受雌激素影响。雌激素以何种方式 对喉突触的作用将促进神经递质的释放 雌激素作用的细胞和分子机制研究 通过激素消融和修复，免疫细胞化学和 原位杂交。一种喉特异的雄激素调节的肌球蛋白 重链基因(Lm)被认为是一种强有力的分子候选基因 用于调节喉部的纤维类型。土地管理在中国的作用 纤维类型的测定将在体内和体外使用 分子和组织学方法。初步结果表明，Lm 是一种胚胎肌球蛋白重链(MHC)亚型。Lm和Lm的表达 其他非洲爪哇的MHC将在组织提取液中进行检查，整装 以及使用杂交技术的切片。Lm和其他MHC的 雄激素和甲状腺激素在喉部肌肉中的作用 体内和体外采用内分泌消融和置换。的血统 将对产生喉纤维的成肌细胞进行检查，并探讨 肌成肌细胞在纤维类型转换中表达Lm。

The goal of this research is an understanding of how hormones, particularly the steroids - androgens and estrogens, control the sexually specific development of target neurons and muscle to produce the mature male or female phenotype. These questions are central to an understanding of male- and female-typical clinical disorders. Hormone-directed cell development underlies malignancies of prostate and breast, disorders of secondary sexual differentiation such as androgen-insensitivity and pseudohemaphodism and at least some aspects of the establishment of gender identity. This proposal is focussed on the control of cell type in laryngeal muscle fibers and at the laryngeal neuromuscular junction of Xenopus laevis. This experimental preparation provides an excellent model system in which to study the cellular and molecular bases of secondary sexual differentiation. The development of the vocal organ, or larynx, is highly sexually dimorphic as a result of sex differences in the endocrine milieu. The isolated larynx can produce actual vocalizations permitting identification of male- and female-specific electrophysiological and muscular characteristics which underlie the different vocal repertoires of adult males and females. These differences include a sex difference in synaptic efficacy - weak synapses in males versus strong synapses in female - and in muscle fiber type -rapidly contracting fibers in males and slowly contracting fibers in females. The control of synaptic strength and the ability of synapses to increase in efficacy with use will be examined in males and female larynges using electrophysiological and dye imaging methods. Calcium entry into the presynaptic terminal will be followed using calcium-sensitive, fluorescent dyes; mechanisms underlying sex differences - including sex differences in ion channels and in other aspects of transmitter release- will be examined. The developmental origins of sex differences in synaptic efficacy will be explored. Preliminary results strongly suggest that sex differences in synaptic strength are regulated by exposure to estrogen. The way in which estrogen acts on the laryngeal synapse to promote neurotransmitter release will be studied and cellular and molecular mechanisms underlying estrogen action determined using hormone ablation and restoration, immunocytochemistry and in situ hybridization. A laryngeal-specific, androgen-regulated myosin heavy chain gene (LM) has been identified as a strong molecular candidate for the regulation of fiber type in the larynx. The role played by LM in fiber type determination will be examined in vivo and in vitro using molecular and histological approaches. Preliminary results suggest that LM is an embryonic myosin heavy chain (MHC) isoform. The expression of LM and of other Xenopus MHC's will be examined in tissue extracts, whole mounts and sections using hybridization techniques. The of LM and of other MHC's in laryngeal muscle by androgen and thyroid hormone will be explored in vivo and in vitro using endocrine ablation and replacement. The lineage of myoblasts giving rise to laryngeal fibers will be examined and the role of LM-expressing myoblasts in fiber type switching examined.