Suprapontine Control of Micturition

描述(申请人提供)：尿液的储存和周期性释放是从中枢神经系统(CNS)的几个层次控制的，包括腰椎脊髓、脑桥、下丘脑、皮质下核和大脑皮层。各种证据表明，排尿反射的兴奋性副交感神经成分依赖于起源于脑桥(“桥脑排尿中心”-PMC)的脊髓上通路，并将下行纤维发送到骶髓。 本提案中概述的研究旨在利用现代神经解剖学、神经相学和神经生理学技术，对调节排尿反射通路的桥脑和桥上结构进行详细分析。这项拟议的研究的目的是：1)利用电刺激，确定大脑皮层、下丘脑和邻近下丘脑的区域中调节膀胱反射的部位。2)观察电刺激阳性反应(抑制或易化)部位微量注射L-谷氨酸的作用。3)详细研究下丘脑和皮质部位对等长节律性膀胱收缩的调节作用，b)排尿测膀胱图(CMG)，c)经下腹神经对膀胱的交感神经传入，d)尿外括约肌肌电图，e)盆神经刺激诱发的反射活动，f)PMC和盆神经传出水平的单单位和多单位活动。4)利用免疫组织化学技术确定可能通过桥上神经递质调节的神经递质，并在这些研究之后进行神经药理学研究，以确定这些可能的神经递质的激动剂，特别是拮抗剂对调节作用的影响。5)确定电刺激膀胱传入时，桥脑和桥上结构(特别是皮质和下丘脑)中表达癌基因C-LOS的神经元的位置。在这项研究中获得的信息不仅将为排尿途径提供一个更完整的线路图，而且还可能建议对排尿行为进行可能的药物修饰。

DESCRIPTION (provided by applicant): The storage and periodic release of urine is controlled from several levels of the central nervous system (CNS) including the lumbosacral spinal cord, rostral pons, hypothalamus, subcotical nuclei, and the cerebral cortex. Various evidence indicates that the excitatory parasympathetic component of the mictudtion reflex is dependent upon supraspinal pathway originating in the rostral pons ("pontine micturition center" - PMC) and sending descending fibers to the sacral spinal cord. The studies outlined in the present proposal are designed to provide a detail analysis, using modem neuroanatomical, neurophar macological and neurophysisological techniques, of pontine and suprapontine structures which modulate the micturition reflex pathway. The aims of this proposed research are: 1) To determine, using electrical stimulation, sites within the cortex, hypothalamus, and areas adjacent to hypothalamus which modulate bladder reflexes. 2) To examine the effects of L-glutamate microinjected into those sites which give positive results (either inhibition or facilitation) with electrical stimulation. (L-glutamate witl be used here as pharmacological tool to determine whether cell bodies or axons-in-passage are being activated by the electrical stimulation - L-glutamate being active only at cell bodies.) 3) To study in detail the modulation by hypothalamic and cortical sites on: a) isometric rhythmic bladder contractions, b) voiding cystometrogram (CMG), c) sympathetic input to bladder via the hypogastric nerve, d) electromyogram (EMG) of the external urethral sphincter, e) reflex evoked activity to pelvic nerve stimulation and f) single and multiunit activity at the level of the PMC and pelvic nerve efferents. 4) To determine using immunohistochemical techniques the possible neurotransmitters which mediate modulation by these suprapontine sites, and to follow these studies with neuropharmacological studies to determine the effects of agonist and especially antagonist of these putative neurotransmitters mediating the modulatory effects. 5) To determine the location of neurons in pontine and suprapontine structures (especially cortical and hypothalamic sites) which express the oncogene C-los to electrical stimulation of bladder afferents. The information gained in this study will not only provide a much more complete wiring diagram for the micturition pathway but may also suggest possible pharmacological modification of the act of micturition.