Afferent synaptic transmission in the mammalian cochlea

哺乳动物耳蜗中的传入突触传递

• 批准号: 6839464
• 负责人: ELISABETH GLOWATZKI
• 金额: $ 30.16万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6839464
• 关键词: afferent nerve; calcium flux; cochlea; cochlear nerve; ear hair cell; laboratory mouse; laboratory rat; membrane potentials; neural transmission; neuroregulation; voltage /patch clamp; voltage gated channel

DESCRIPTION (provided by applicant): This proposal focuses on investigating the mechanism of synaptic transmission at the inner hair cell (IHC) afferent synapse in the mammalian cochlea. This most peripheral chemical synapse in the auditory pathway serves as an interpreter translating the hair cell receptor potential into a train of excitatory postsynaptic potentials that activate action potentials in the afferent auditory nerve fibers. The specific features of the IHC afferent synapse critically determine how a sound signal is coded in the inner ear and transmitted to the brain via auditory nerve fiber activity. Our aim is to characterize pre- and postsynaptic mechanism that shape the postsynaptic activity in IHC afferent fibers. We will record postsynaptic activity using the whole cell patch clamp method. The recording sites will be the afferent fiber terminal directly at the inner hair cell synapse and the afferent fiber soma in the spiral ganglion in excised preparations of rat and mouse cochleae. To exactly describe the relationship between presynaptic stimulus and postsynaptic activity, we will make double recordings from IHCs and afferent fiber terminals. To affect transmitter release and define the quantal size, we will record excitatory postsynaptic currents and vary experimental conditions; i.e. changing the temperature or ionic environment and using release-affecting toxins. To understand postsynaptic determinants of synaptic transmission, we will provide a basic description of the waveform of the excitatory postsynaptic potential and its relation to the activation of action potentials. Using pharmacological tools, we will try to identify individual components that shape the postsynaptic potential waveform starting with a focus on different classes of potassium channels. We will also study the role of efferent inputs onto afferent fiber activity. Most recordings will be performed in the already established preparation using postnatal cochleae. In parallel we will extend our recordings to mature cochleae, as our ultimate aim is to understand both development and adult function of the IHC afferent synapse. These studies will further our knowledge of basic mechanisms of peripheral hearing and therefore also will lead to a better understanding of abnormal hearing and deafness.

描述（由申请人提供）：该提案重点是研究哺乳动物耳蜗中内毛细胞（IHC）传入突触的突触传播机制。在听觉途径中，这种最外围化学突触是将毛细胞受体电势转化为兴奋性突触后电位的列车的解释器，这些兴奋性突触后电势会激活传入的听觉神经纤维中的动作电位。 IHC传入突触的特定特征批判性地决定了声音信号在内耳中的编码方式，并通过听觉神经纤维活动传播到大脑。 我们的目的是表征塑造IHC传入纤维中突触后活性的突触前和后机制。我们将使用整个细胞斑块夹方法记录突触后活动。记录位点将是内部毛细胞突触的传入纤维末端，在螺旋神经节中的传入纤维体中，在切除的大鼠和小鼠耳蜗的干燥制剂中。为了准确描述突触前刺激与突触后活性之间的关系，我们将从IHC和传入纤维末端进行双重记录。为了影响发射机释放并定义量化大小，我们将记录兴奋性的突触后电流和不同的实验条件。即改变温度或离子环境并使用释放影响的毒素。为了了解突触传播的突触后决定因素，我们将提供兴奋性突触后潜力波形及其与动作电位激活的关系的基本描述。使用药理学工具，我们将尝试识别塑造突触后电势波形的单个组件，从重点放在不同类别的钾通道上。我们还将研究传出输入到传入纤维活性上的作用。大多数录音都将在已经建立的使用产后Cochleae的准备工作中进行。同时，我们将录音扩展到成熟的耳蜗，因为我们的最终目的是了解IHC传入突触的发展和成人功能。这些研究将进一步了解我们对外围听力的基本机制的了解，因此也将使人们对异常的听力和耳聋有更好的了解。