Neurotransmission at the vestibular calyx synapse

这项建议的目标是了解前庭I型毛细胞/花冠的突触传递。 Synapse。在羊膜突起和椭圆囊中已描述了三种形态传入。 花萼单位只接触I型毛细胞(HCI)，Bouton单位仅接触II型毛细胞和二型性 单位接受来自Bouton纤维和花萼纤维的神经支配(Goldberg，2000)。生理反应 这三类纤维的动力学各不相同，其中花萼单位具有最不规则的放电模式 旋转刺激的最低增益(Baird等人1988年；Lysakowski等人。1995年)。产生这些差异的原因 尚不清楚，但假设包括毛细胞机械-电转导(MET)的差异。 特性&初级前庭传入的生物物理膜特性的差异。我们会 研究Hci和相关的花冠传入，以确定这个独特的终末的放电模式是如何由 突触前和突触后的机制。在目标1中，膜片钳技术将被用于研究离子 一种新开发的隔离花萼末端制备方法中的电导和递质释放 来自沙土鼠前庭器官的人机界面(Rennie&Streeter，2006)。兴奋性突触后电流 毛细胞递质释放的结果将在各种条件下从花萼终端记录下来。 在目标2中，我们将记录毛束移位期间来自HCI的MET电流和感受器电位 在一个完整的椭圆形制剂中使用了一个僵硬的探头。在目标3中，数学建模技术将是 用于模拟HCI和花萼对谷氨酸的反应。花萼的无源电学性质& 在神经元编程中，将使用分段计算模型来模拟附着的轴突 环境。钠、钙和钾通道将用霍奇金-赫胥黎式速率常数建模，使用 在AIMS 1和AIMS 2中获得的实验数据。将使用遗传算法来优化动力学 离子电导的激活和失活参数。头晕是最常见的一种 医疗投诉。了解平衡感觉的基本细胞机制对于 确定这种衰弱状况的原因和治疗方法的基础工作。实验与实验相结合 &建模方法将阐明感觉信息是如何由HC1转化为 通过它们的传入进行神经编码。

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.