CELLULAR MECHANISMS OF RESPIRATORY NETWORK MODULATION

多功能神经网络是各种节律行为的基础，虽然解剖学上是硬连接的，但它们在功能上是灵活的。本提案探讨了哺乳动物呼吸系统中灵活性的细胞机制。一个重要的呼吸调节因子是氧含量。在体内，呼吸系统对反复低氧发作的反应是一种长期持续的呼吸活动促进（LTF），依赖于血清素。在本提案中：(1)我将确定在低氧发作后，孤立的节律性脑干切片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查呼吸网络和运动神经元活动以及呼吸频率的长期变化。我将使用药理学技术来确定LTF是否依赖于血清素。(3)我将通过使用电流和电压钳记录来确定呼吸网络神经元的破裂特性、离子通道和/或突触传递是否有变化，从而确定LTF的细胞机制。这项工作将增加我们对呼吸网络调节的认识，并有助于我们对睡眠呼吸暂停等疾病的理解，因为人们认为，在低氧期后，对呼吸系统的血清素能驱动的增强可能是对睡眠呼吸暂停发作的反应。

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.