Neurotransmission at the vestibular calyx synapse

前庭萼突触的神经传递

• 批准号: 7367315
• 负责人: Katherine Janet Rennie
• 金额: $ 10万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-04 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7367315
• 关键词: AMPA Receptors; Action Potentials; Address; Adult; Axon; Cells; Characteristics; Chemicals; Chromosome Pairing; Class; Code; Computer Simulation; Condition; Crista ampullaris; Data; Disease; Dizziness; Environment; Equilibrium; Esthesia; Experimental Models; Fiber; Fire - disasters; Frequencies; Gated Ion Channel; Genetic Programming; Gerbils; Glutamate Receptor; Glutamates; Goals; Hair; Hair Cells; Hodgkin Disease; Injection of therapeutic agent; Ion Channel; Kinetics; Ligands; Measures; Mediating; Medical; Membrane; Modeling; Movement; Neurons; Organ; Patch-Clamp Techniques; Pattern; Perfusion; Pharmacological Treatment; Physiological; Potassium Channel; Preparation; Process; Property; Rate; Rennie; Reporting; Resistance; Rodent; Role; Sensory; Shapes; Signal Transduction; Simulate; Stereocilium; Stimulus; Synapses; Synaptic Transmission; System; Techniques; Testing; Turtles; Type I Hair Cell; Type II Hair Cell; Utricle structure; Variant; base; computerized data processing; electrical property; extracellular; mathematical model; nerve supply; neurotransmission; neurotransmitter release; novel; patch clamp; postnatal; postsynaptic; programs; quantum; receptor; receptor coupling; relating to nervous system; response; simulation; size; transmission process; voltage; voltage clamp

The goal of this proposal is to understand synaptic transmission at the vestibular type I hair cell/calyx synapse. Three classes of morphological afferents have been described in the amniote crista and utricle. Calyx units contact type I hair cells (HCI) exclusively, bouton units contact type II hair cells only & dimorphic units receive innervation from both bouton & calyx fibers (Goldberg, 2000). The physiological response dynamics of these three classes of fibers vary, with calyx units having the most irregular firing pattern & the lowest gains to rotational stimuli (Baird et al. 1988; Lysakowski et al. 1995). The reasons for these variations are unclear, but are hypothesized to include differences in hair cell mechano-electrical transduction (MET) properties & differences in the biophysical membrane properties of primary vestibular afferents. We will study HCI & associated calyx afferents to determine how firing patterns in this unique terminal are shaped by both pre- & post-synaptic mechanisms. In Aim 1, patch clamp techniques will be used to study ionic conductances & transmitter release in a newly developed preparation of calyx terminals isolated together with HCI from gerbil vestibular organs (Rennie & Streeter, 2006). Excitatory postsynaptic currents (EPSCs) resulting from hair cell transmitter release will be recorded from calyx terminals under a variety of conditions. In Aim 2 we will record MET currents & receptor potentials from HCI during displacement of the hair bundle with a stiff probe in a wholemount utricle preparation. In Aim 3, mathematical modeling techniques will be employed to simulate HCI & calyx responses to glutamate. The passive electrical properties of the calyx & attached axon will be simulated with a segmented computational model in the NEURON programming environment. Na+, Ca2+ and K+ channels will be modeled with Hodgkin-Huxley style rate constants using the experimental data obtained in Aims 1& 2. A genetic algorithm wiil be used to optimize the kinetic parameters for the activation & inactivation of ionic conductances. Dizziness is one of the most common medical complaints. Understanding the basic cellular mechanisms of balance sensation is essential to lay the groundwork for identifying causes & cures for this debilitating condition. The combination of experimental & modeling approaches will elucidate how sensory information is transformed by HC1 & converted into a neural code by their afferents.

这个提议的目的是了解前庭I型毛细胞/萼的突触传递 突触三种类型的形态传入已被描述在脊嵴和椭圆囊。 花萼单位接触I型毛细胞（HCI）只，钮扣单位接触II型毛细胞只&二形 单位接受来自扣和萼纤维的神经支配（Goldberg，2000）。的生理反应 这三类纤维的动力学各不相同，花萼单位具有最不规则的燃烧模式， 旋转刺激的增益最低（Baird等人，1988; Lysakowski等人，1995）。这些变化的原因 尚不清楚，但假设包括毛细胞机械电转导（MET）的差异 初级前庭传入的生物物理膜特性的差异。我们将 研究HCI和相关的花萼传入，以确定如何在这个独特的终端放电模式是由形状 突触前和突触后机制。在目标1中，膜片钳技术将用于研究离子 电导和发射器释放在一个新开发的制备花萼终端隔离在一起 用来自沙鼠前庭器官的HCI（Rennie & Streeter，2006）。兴奋性突触后电流 在各种条件下，将从花萼末端记录毛细胞释放的递质。 在目标2中，我们将记录毛束移位期间HCI的MET电流和受体电位 在一个完整的椭圆囊标本中用一个硬探针。在目标3中，数学建模技术将 用于模拟HCl和花萼对谷氨酸的反应。花萼的被动电特性& 在NEURON编程中，使用分段计算模型模拟附着轴突 环境Na+、Ca 2+和K+通道将使用Hodgkin-Huxley式速率常数建模， 目标1和2中获得的实验数据。采用遗传算法对动力学参数进行优化 用于离子电导的激活和失活的参数。头晕是最常见的 医疗投诉了解平衡感觉的基本细胞机制对于奠定 确定原因的基础&治疗这种衰弱的条件。结合实验 和建模方法将阐明感觉信息是如何被HC 1转化并转化为一个 通过传入神经进行编码