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）：本提案重点研究哺乳动物耳蜗内毛细胞（IHC）传入突触的突触传递机制。听觉通路中最外周的化学突触充当解释器，将毛细胞受体电位翻译成一系列兴奋性突触后电位，激活传入听觉神经纤维中的动作电位。 IHC 传入突触的具体特征关键决定了声音信号如何在内耳中编码并通过听觉神经纤维活动传输到大脑。 我们的目标是表征影响 IHC 传入纤维突触后活动的突触前和突触后机制。我们将使用全细胞膜片钳方法记录突触后活动。记录位点将是大鼠和小鼠耳蜗切除标本中直接位于内毛细胞突触处的传入纤维末端和螺旋神经节中的传入纤维胞体。为了准确描述突触前刺激和突触后活动之间的关系，我们将从 IHC 和传入纤维末端进行双重记录。为了影响递质释放并定义量子大小，我们将记录兴奋性突触后电流并改变实验条件；即改变温度或离子环境并使用影响释放的毒素。为了了解突触传递的突触后决定因素，我们将对兴奋性突触后电位的波形及其与动作电位激活的关系进行基本描述。使用药理学工具，我们将尝试识别形成突触后电位波形的各个成分，首先关注不同类别的钾通道。我们还将研究传出输入对传入纤维活动的作用。大多数录音将使用出生后耳蜗在已经建立的准备中进行。与此同时，我们将把录音扩展到成熟的耳蜗，因为我们的最终目标是了解 IHC 传入突触的发育和成年功能。这些研究将进一步加深我们对周围听力基本机制的了解，从而更好地了解听力异常和耳聋。