CELLULAR MECHANISMS OF RESPIRATORY NETWORK MODULATION

呼吸网络调节的细胞机制

• 批准号: 2796056
• 负责人: DAWN MARIE BLITZ
• 金额: $ 3.03万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2796056
• 关键词: laboratory mouse; neural conduction; neural facilitation; neural information processing; neuropharmacology; pulmonary respiration; respiration regulatory center; respiratory hypoxia; reticular formation; serotonin; serotonin inhibitor; serotonin receptor; synapses; voltage /patch clamp

Multifunctional neural networks underlie a variety of rhythmic behaviors and while anatomically hard-wired, they are functionally flexible. This proposal examines cellular mechanisms of flexibility in the mammalian respiratory system. One important modulator of respiration is oxygen level. In vivo, the respiratory system response to repetitive episodes of low oxygen, is a long lasting facilitation (LTF) of respiratory activity that is serotonin dependent. In this proposal: (1) I will determine if the respiratory system in the isolated rhythmic brain stem slice also expresses LTF following episodes of low oxygen. I will use whole cell patch clamp recordings to examine long term changes in activity of respiratory network and motor neurons as well as respiratory frequency. (2) I will use pharmacological techniques to determine if the LTF is serotonin dependent. (3) I will determine cellular mechanisms underlying LTF by using current and voltage clamp recordings to determine if there are changes in bursting properties, ion channels and/or synaptic transmission in respiratory network neurons. This work will increase our knowledge of respiratory network modulation, and will contribute to our understanding of disorders such as sleep apnea, since it is thought an enhancement of serotonergic drive to the respiratory system following periods of low oxygen may be a response to sleep apnea episodes.

多功能神经网络是各种节律行为的基础，虽然在解剖学上是硬连接的，但它们在功能上是灵活的。这项建议研究了哺乳动物呼吸系统中灵活性的细胞机制。氧气水平是调节呼吸的一个重要因素。在体内，呼吸系统对反复低氧的反应是一种长期的呼吸活动促进(LTF)，这是依赖于5-羟色胺的。在这项建议中：(1)我将确定在低氧发作后，分离的节律性脑干切片中的呼吸系统是否也表达LTF。我将使用全细胞膜片钳记录来检测呼吸网络和运动神经元活动的长期变化以及呼吸频率。(2)我将使用药理学技术来确定LTF是否依赖于5-羟色胺。(3)我将通过使用电流和电压钳记录来确定LTF背后的细胞机制，以确定呼吸网络神经元的爆发特性、离子通道和/或突触传递是否发生变化。这项工作将增加我们对呼吸网络调节的了解，并将有助于我们对睡眠呼吸暂停等疾病的理解，因为人们认为低氧后呼吸系统5-羟色胺能驱动的增强可能是对睡眠呼吸暂停发作的反应。