ORGANIZATION OF MALE REPRODUCTIVE NEURAL CIRCUITS

描述：(改编自申请人的摘要) 这项研究的目的是阐明神经机制，通过 特定的前脑、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， 前脑通路对L6/S1脊髓的影响。这条线路 包括MPO--&GT；PGI--&GT；脊髓。巨细胞旁核 延髓腹外侧区(PGI)接受MPO的直接输入 并大量投射到L6/S1索上。我们的初步数据显示， 来自PGi的下行投影选择性地终止于 支配骨盆内脏的运动神经元池。AIM 1将测试 假设MPO投射的目标是投射到 腰骶部脊髓。使用Antero和Antero的组合方法 将使用逆行示踪剂来描绘解剖组织 MPO--&gt；PGi--&gt；脊髓回路。脊椎性反射在 强直向下抑制，可能是通过PGI的输入。近期 研究表明，对于正常男性来说，MPO神经元的活性必须增加 生殖行为才会发生。因此，我们假设增加了 MPO在交配前和交配过程中的活动，部分是为了减少 脊髓运动的紧张性抑制(去抑制假说) 条件反射。Aim 2采用协调神经解剖学、免疫细胞化学 和电生理技术来测试这种解除抑制 假设：MPO激活抑制PGI--&GT；脊髓神经元允许 以脊椎为媒介的性反射的发生。MPO及其输出 是启动和维持男性性行为的中心 行为。Aim 3测试MPO--&gt；PGi电路是 在男性性行为中选择性地参与；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 对GABA的影响。由于交配是一种类固醇依赖的行为，我们预测 MPO--&gt；PGi--&gt；脊髓的关键神经基质 环路将包含性腺类固醇的受体。这些研究将 首次提供MPO--&gt；pgi--&gt；脊柱的功能特征 脐带通路。总之，这些研究将提供详细的解剖结构 以及调节男性性行为的神经回路上的生理数据。

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.