ORGANIZATION OF MALE REPRODUCTIVE NEURAL CIRCUITS

描述：（改编自申请人摘要） 这项研究的目的是阐明神经机制， 特定前脑、脑干和脊髓部位协调男性 生殖行为我们新的初步研究表明 介导前脑对L6/S1脊髓影响的通路。该电路 包括MPO-> PGi->脊髓。旁巨细胞 (PGi)延髓腹外侧区接受髓过氧化物酶的直接输入 并严重突出到L6/S1脊髓。初步数据显示， 来自PGi的下降突起选择性地终止于 支配盆腔内脏的运动神经元池。目标1将测试 假设MPO投射靶向PGi神经元，其投射到 腰骶脊髓一种结合使用analog和 逆行示踪剂将用于描绘解剖组织 MPO-> PGi->脊髓回路。脊髓性反射低于 紧张性下行抑制，大概是通过输入从PGi。最近 研究表明，对于正常男性，MPO神经元活性必须增加， 生殖行为发生。因此，我们假设， MPO活性在交配前和交配期间的功能，部分， 脊髓运动紧张性抑制（"去抑制假说 反射目的2采用协调的神经解剖学，免疫细胞化学 和电生理技术来测试这种抑制解除 假设：MPO激活抑制PGi-->脊髓神经元， 脊椎介导的性反射才能发生MPO及其输出 是启动和维持男性性别的核心 行为目的3检验MPO--> PGi回路是 在男性性行为中有选择地参与;激活这一回路 在交配过程中通过释放PGi抑制阴部前运动神经元 的GABA。由于交配是一种类固醇依赖行为，我们预测， 沿着沿着这个MPO--> PGi-->脊髓的关键神经基质 电路将包含性腺类固醇的受体。这些研究将 提供MPO-> PGi->脊髓的第一个功能特征 脊髓通路总之，这些研究将提供详细的解剖 以及调节男性性行为的神经回路的生理数据。

DESCRIPTION: (Adapted From The Applicant's Abstract) The goal of this research is to elucidate the neural mechansims by which specific forebrain, brainstem and spinal cord sites coordinate male reproductive behavior. Our new preliminary studies suggest a potential pathway that mediates forebrain influences on L6/S1 cord. This circuit comprises the MPO-->PGi-->spinal cord. The nucleus paragigantocellularis (PGi) in the ventrolateral medulla receives direct input from the MPO and projects heavily to the L6/S1 cord. Our preliminary data show that descending projections from the PGi selectively terminate within the motoneuronal pools that innervate the pelvic viscera. Aim 1 will test the hypothesis that MPO projections target PGi neruons that project to the lumbosacral spinal cord. A combined approach using both antero and retrograde tracers will be used to delineate the anatomical organization of MPO-->PGi-->spinal cord circuit. Spinal sexual reflexes are under tonic descending inhibition, presumably via input from the PGi. Recent studies suggest that MPO neuronal activity must increase for normal male reproductive behavior to occur. We postulate therefore that increased MPO activity before and during copulation functions, in part, to reduce the tonic inhibition ("disinhibition hypothesis") on spinal motor reflexes. Aim 2 employs coordinate neuroanatomical, immunocytochemical and electrophysiological techniques to test this disinhibition hypothesis: MPO activation inhibits PGi-->spinal cord neurons allowing for spinally mediated sexual reflexes to occur. The MPO and its output to the PGi are central for the initiation and maintenance of male sex behavior. Aim 3 tests the hypothesis that the MPO-->PGi circuit is selectively engaged during male sex behavior; activation of this circuit during copulation inhibits PGi pudendal premotor neurons via the release of GABA. As copulation is a steroid dependent behavior, we predict that the critical neural substrates along this MPO-->PGi-->spinal cord circuit will contain receptors for gonadal steroids. These studies will provide the first functional characterization of the MPO-->PGi-->spinal cord pathway. Together, these studies will provide detailed anatomical and physiological data on a neural circuit regulating male sex behavior.