CSF AND THE CENTRAL CHEMICAL CONTROL OF BREATHING

呼吸的控制包括脑干节律和模式发生器。 它们的正常功能依赖于机械和化学传入 信息包括二氧化碳和/或H+传感中心的信息 化学感受器。该项目将描述他们的位置，类型 单个单位参与，以及化疗敏感性的机制。一种新的 方法，1毫升注射乙酰唑胺，产生一个有限制的 持续性脑干组织酸中毒区域(半径350微米) 麻醉的老鼠和猫。网站(以荧光微珠标记)位于 哪种乙酰唑胺注射剂可增强膈神经的活性 化学感受器的位置(我们目前至少知道3个)。这个探头 与多管吸管一起使用进行记录和注射将允许 单细胞化学敏感单位的鉴定 乙酰唑胺所致组织酸中毒及其体内检测 化学感受器机制包括突触的作用，咪唑- 组氨酸、乙酰胆碱酯酶和碳酸氢盐/氯的逆向转运蛋白。 正常的化疗敏感性需要后梯形结构的完整性 延髓头端腹外侧区腹侧核(RTN) 至吻部和中间部交界处的面神经核 化学敏感区。RTN在控制以下方面具有独特的重要性 麻醉动物单侧RTN毁损取消呼吸 对化学药物敏感，常对呼吸暂停有抑制作用。这个项目 将评估RTN区域的功能和重要性。会的 用逆行解剖学方法描述延髓核传入神经的来源 示踪剂和评价RTN在刺激反应中的作用 中枢和外周化学感受器和上呼吸道感受器 喉上传入神经。使用多管吸量管 录制和注入我们将确定受影响的RTN单元类型 每个传入神经和涉及的神经递质。的传出效应 RTN刺激对三大类呼吸相关脑干的影响 将评估神经元及其在长期促进中的作用， 某些形式的心绞痛所见的持续的膈活动增加 刺激。单边RTN改变的效果如何？ 就像它在有意识的动物中的作用一样被研究。 对中枢化学接收和这个小区域的进一步了解 它的破坏可以取消化学接收并导致呼吸暂停，是 重要的是要有一个完整的理解正常的生理 对呼吸的控制。这在慢性疾病等情况下可能很重要。 阻塞性肺病的呼吸系统控制系统经常 决定适应性反应与婴儿猝死综合征 其中化疗敏感性异常是一种病因学假说 最近的研究表明，在两名人类受害者中，神经元发育不良 延髓区域，类似于大鼠和猫的RTN区域。

The control of breathing involves brainstem rhythm and pattern generators which depend, for normal function, on mechanical and chemical afferent information including that of CO2 and/or H+ sensing central chemoreceptors. This project will describe their locations, the type of single unit involved, and the mechanism of chemosensitivity. A new approach, a 1 nl injection of acetazolamide, produces a circumscribed region of lasting brainstem tissue acidosis (<350 micro in radius) in anesthetized rats and cats. Sites (marked by fluorescent microbeads) at which acetazolamide injection increases phrenic activity identify a chemoreceptor location (we know of at least 3 at present). This probe used with a multi-barrelled pipette for recording and injecting will allow identification of single chemosensitive units within the sphere of acetazolamide induced tissue acidosis and examination in vivo of chemoreceptor mechanisms including the role of synapses, imidazole- histidine, acetylcholinesterase, and the bicarbonate/chloride antiporter. Normal chemosensitivity requires the integrity of the retrotrapezoid nucleus (RTN), a region of the rostral ventrolateral medulla lying ventral to the facial nucleus at the border of the rostral and intermediate chemosensitive areas. The RTN has singular importance in the control of breathing for in anesthetized animals unilateral RTN destruction abolishes chemosensitivity and depresses respiration often to apnea. This project will evaluate the function and importance of the RTN region. It will describe the sources of afferents to the RTN using retrograde anatomical tracers and evaluate the role of the RTN in responses to stimulation of central and peripheral chemoreceptors and to upper airway receptors with superior laryngeal afferents. Using multi-barrelled pipettes for recording and injecting we will determine the RTN unit types affected by each afferent and the neurotransmitter involved. The efferent effects of RTN stimulation on the three major groups of respiratory related brainstem neurons will be evaluated as well as its role in long term facilitation, the prolonged increase of phrenic activity seen with certain forms of stimulation. How unilateral RTN alterations are so effective will be examined as will its role in conscious animals. Further knowledge of central chemoreception and this small region, the destruction of which can abolish chemoreception and result in apnea, is important for having a complete understanding of the normal physiology of the control of breathing. It may be important in situations like chronic obstructive lung disease where the respiratory control system often determines the adaptive response and the Sudden Infant Death Syndrome where abnormalities in chemosensitivity are one etiological hypothesis and recent work has shown, in two human victims, neuronal hypoplasia in a medullary region analogous to the RTN region in rat and cat.