Neurotransmission at the vestibular calyx synapse

前庭萼突触的神经传递

• 批准号: 7596253
• 负责人: Katherine Janet Rennie
• 金额: $ 25.69万
• 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: 2007-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7596253
• 关键词: AMPA Receptors; Action Potentials; Address; Adult; Axon; Cells; Characteristics; Chemicals; Code; Computer Simulation; Crista ampullaris; Data; Disease; Dizziness; Environment; Equilibrium; Esthesia; Experimental Models; Fiber; 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; Rennie; Reporting; Research Personnel; 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; transmission process; voltage; voltage clamp

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：该提案的目的是了解前庭I型毛细胞/花萼突触的突触传播。在羊膜Crista和Utricle中已经描述了三类的形态传入。花萼单元专门接触I型毛细胞（HCI），Bouton单元仅接触II型毛细胞和双态单元，并从Bouton＆Calyx纤维接收神经（Goldberg，2000）。这三类纤维的生理反应动力学变化，花萼单元具有最不规则的放电模式，并且对旋转刺激的增长最低（Baird等，1988; Lysakowski etal。1995）。这些变化的原因尚不清楚，但假设包括毛细胞机械电源转导（MET）特性的差异和差异，以及原发性前庭传统的生物物理膜性质的差异。我们将研究HCI和相关的花萼传入，以确定这种独特末端的发射模式如何受到突触前和突触后机制的影响。在AIM 1中，将使用斑块夹技术来研究与来自Gerbil前庭器官的HCI一起新开发的Calyx端子的新制备的离子电导和发射器释放（Rennie＆Streeter，2006年）。在多种条件下，将记录由花萼末端记录毛细胞发射器引起的兴奋性突触后电流（EPSC）。在AIM 2中，我们将记录HCI的MET电流和受体电位在头发束的位移期间，并在整个尿素制剂中用硬探针进行僵硬的探针。在AIM 3中，将采用数学建模技术来模拟HCI和花萼对谷氨酸的反应。花萼和连接的轴突的被动电性能将通过神经元编程环境中的分段计算模型进行模拟。 Na+，Ca2+和K+通道将使用AIMS 1＆2中获得的实验数据对Hodgkin-Huxley样式速率常数进行建模。用于优化动力学参数的遗传算法，以优化激活和灭活离子电导的参数。头晕是最常见的医疗投诉之一。了解平衡感的基本细胞机制对于确定这种衰弱状况的原因和治愈的基础至关重要。实验和建模方法的组合将阐明HC1转化感官信息并被其传入转化为神经代码。