CONTROL OF GASTROINTESTINAL ELIMINATIVE REFLEXES

建议结合生理学和解剖学研究， 研究延髓中缝和下丘脑在 控制胃肠消除反射回路。 的影响 中缝隐核/苍白核的电和化学刺激 (nRO/nRP）和下丘脑室旁核（PVN）， 将检查猫的肛门外括约肌（EAS）。 微量注射肽（催产素[OXY]）和加压素[AVP]）， 促甲状腺激素释放激素（TRH）和5-羟色胺（5-HT）进入Onuf's 核将被用来评估内源性配体的影响， 下行系统对EAS音调、直肠肛门反射和EAS运动神经元的影响 (MN)兴奋性 5-HT、OXY和AVP的拮抗剂将用于 试图扭转刺激的效果。 从nRO/nRP（和相邻结构）到PVN的下降投影 骶髓中的Onuf核，其中包含MN 支配EAS，将研究与跟踪技术，电子 显微镜（EM）和免疫组织化学（IHC）。 我们的假设是 这些下行的输入与近端的 括约肌神经元的树突和胞体。 解剖学数据强烈表明 这些脊髓副交感神经/躯体神经网络 与副交感神经/躯体神经的结构和功能相似 控制脑中的神经回路 总之，这些研究应该提供一个解剖和功能， 分析一些中央电路负责 前脑/脑干下行控制远端肠排除反射 并且可以允许与这样的近端肠反射的控制进行比较， 我们非常熟悉的。 此外，拟议的研究可能会产生 尿失禁的病因学的见解与 胃肠道疾病、神经系统疾病（如自主神经系统疾病）、 失败中风，和脊髓创伤），和老化，并将增加 关于一种独特的运动神经元类型的信息， 疾病如ALS。

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.