CONTROL OF GASTROINTESTINAL ELIMINATIVE REFLEXES

建议进行生理学和解剖学研究相结合的研究 探讨延髓中缝和下丘脑在脑损伤中的作用 控制胃肠排泄反射回路。其影响 电和化学刺激中缝隐核/苍白球 (NRO/NRP)和下丘脑室旁核 将在猫身上检查肛门外括约肌(EAS)。 微量注射多肽(催产素和加压素[AVP])， 促甲状腺激素释放激素和5-羟色胺 核将被用来评估内源性配体的作用 EAS音调、直肠-肛门反射和EAS运动神经元的下行系统 (M)兴奋性。5-羟色胺、氧和AVP的拮抗剂将用于 试图逆转刺激的效果。 从NRO/NRP(和相邻结构)到PVN的下降投影 Onuf氏核位于脊髓内，内含MNS 将用示踪技术、电子 光镜(EM)和免疫组织化学(IHC)。我们的假设是 这些下行输入与近端的突触直接接触 括约肌MNS的树突和体细胞。解剖学数据强烈表明 这些脊髓副交感神经/躯体网络共享许多 在结构和功能上与副交感/躯体相似 延髓中的控制电路。 总而言之，这些研究应该提供一个解剖和功能 分析了一些负责的中央电路 前脑/脑干下行控制远端肠道消除反射 并可以与近端肠道反射的这种控制进行比较 这是我们非常熟悉的。此外，拟议的研究可能会产生 对与以下疾病相关的大小便失禁病因的见解 胃肠道疾病、神经紊乱(如自主神经 衰竭、中风和脊髓损伤)，以及衰老，并将增加 关于一种独特的运动神经元类型抵抗运动神经元的信息 像肌萎缩侧索硬化症这样的疾病。

A combination of physiological and anatomical studies are proposed to investigate the role of the medullary raphe and the hypothalamus in controlling gastro-intestinal eliminative reflex circuits. The effects of electrical and chemical stimulation of nucleus raphe obscuras/pallidus (nRO/nRP) and the paraventricular nucleus (PVN) of the hypothalamus on the external anal sphincter (EAS) will be examined in the cat. Microinjection of peptides (oxytocin [OXY]) and vasopressin [AVP]), thyrotropin releasing hormone (TRH) and serotonin (5-HT) into Onuf's nucleus will be used to assess the effects of endogenous ligands of the descending systems on EAS tone, recto-anal reflexes, and EAS motoneuron (MN) excitability. Antagonists to 5-HT, OXY and AVP will be used to attempt to reverse the effects of stimulation. Descending projections from nRO/nRP (and adjacent structures) an PVN to Onuf's nucleus in the sacral spinal cord, which contains the MNs innervating the EAS, will be studied with tracing techniques, electron microscopy (EM), and immunohistochemistry (IHC). Our hypothesis is that these descending inputs make direct synaptic contacts with the proximal dendrites and somata of sphincter MNs. Anatomical data strongly suggest that these spinal cord parasympathetic/somatic networks share a number of structural and functional similarities with parasympathetic/somatic control circuits in the medulla. Together, these studies should provide an anatomical and functional analysis of some of the central circuits responsible for forebrain/brainstem descending control of distal gut eliminative reflexes and may allow comparisons with such control of proximal gut reflexes with which we are very familiar. In addition, the proposed studies may yield insights into the etiology of incontinence associated with gastrointestinal diseases, neurological disorders (such as autonomic failure stroke, and spinal cord trauma), and aging, and will add information concerning a unique motoneuron type resistant to motoneuron diseases like ALS.