Synaptic Determinants of Vestibular Afferent Dynamics

前庭传入动力学的突触决定因素

• 批准号: 8441599
• 负责人: RICHARD D RABBITT
• 金额: $ 42.68万
• 依托单位: MARINE BIOLOGICAL LABORATORY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-03 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8441599
• 关键词: Auditory system; Basic Science; Bathing; Benign paroxysmal positional vertigo; Biomechanics; Brain; Calcium; Calcium Channel; Categories; Cells; Chemicals; Code; Communication; Complex; Dendrites; Detection; Development; Disease; Distal; Electrodes; Elements; Epithelium; Equilibrium; Feedback; Fiber; Frequencies; GABA Receptor; Glutamate Receptor; Glutamates; Goals; Hair; Hair Cells; Health; Hearing; Immunofluorescence Immunologic; In Situ; Individual; Investigation; Ions; Kinetics; Labyrinth; Light; Location; Maps; Measures; Mechanics; Methods; Microelectrodes; Microscopic; Nerve; Nerve Fibers; Organ; Peripheral; Phenotype; Population; Potassium; Process; Property; Proteins; Research; Research Design; Semicircular canal structure; Sensory; Severities; Shapes; Signal Transduction; Site; Spatial Distribution; Stimulus; Symptoms; Synapses; Synaptic Receptors; Synaptic Transmission; Syndrome; System; Testing; Transducers; Trees; Type II Hair Cell; Variant; Visual system structure; cell type; computerized data processing; feeding; gamma-Aminobutyric Acid; lucifer yellow; receptor; relating to nervous system; response; sensor; transmission process; voltage; voltage clamp

DESCRIPTION (provided by applicant): In the vestibular system, as in the auditory and visual systems, stimuli are transduced and neural signals processed prior to transmission to the brain. Our research and that of others has clearly shown that the afferent responses from the semicircular canal deviate from canal biomechanics, and has implicated signal processing by the hair cell-primary afferent synapse in shaping the afferent response. Our overarching hypothesis is that the spatial distribution of an ensemble of transmitter and receptor phenotypes on hair cells and the afferent terminal arbors form processing entities that transform hair cell receptor potentials into the frequency code seen in the nerve discharge. The goal of the proposed research is to measure and quantify the contributions of these entities to the adaptation and frequency-dependent responses of vestibular semicircular canal afferents. We have demonstrated that there are three hair cell transmitter phenotypes: GABAergic, glutamatergic and cells that express both transmitters. We propose that specific combinations of hair cells and afferent terminals operating in feed-forward and feedback configurations dictate the transformation of canal biomechanical responses into the neural codes of individual primary afferent fibers. This proposal focuses on four categories of synaptic and/or extrasynaptic factors putatively involved in signal processing: (1) hair cell transmitter phenotype(s) impinging on a given ending, including the possibility of a diversity of hair cell transmitter phenotypes and post-synaptic receptor distributions interacting at a given terminal, (2) potential feedback between the calyx and hair cell, including feedback from hair cell-released transmitter to the hair cell itself, (3) the rate of transmitter release and subsequent synaptic current dynamics, governed by pre- and post-synaptic ionic currents present at a particular synapse, and (4) the integrative properties of the afferent dendrite. Understanding the complexity of the signal processing performed by afferent terminals is a necessary step toward developing treatments for vestibular disorders. Basic science adds information that is important in understanding normal and abnormal function. Once the precise mechanisms involved in shaping afferent dynamics are more thoroughly understood, appropriate and specific pharmacological agents may be developed to reduce abnormal bursts of afferent neural activity, thereby mitigating the severity of vertiginous symptoms in disorders such as M¿ni¿re's syndrome.

描述（由申请人提供）：在前庭系统中，就像在听觉和视觉系统中一样，刺激在传输到大脑之前被转换并处理神经信号，我们和其他人的研究清楚地表明来自半圆形的传入反应。耳道偏离耳道生物力学，并且暗示了毛细胞初级传入突触在塑造传入反应中的信号处理。毛细胞上的发射器和受体表型的集合以及传入末端乔木形成处理实体，将毛细胞受体电位转换为神经放电中看到的频率代码。拟议研究的目标是测量和量化这些实体对神经放电的贡献。前庭半规管传入神经的适应和频率依赖性反应 我们已经证明存在三种毛细胞递质表型：GABA 能、谷氨酸和表达两种递质的细胞。在前馈和反馈配置中操作的传入终端决定了神经管生物力学反应到单个初级传入纤维的神经编码的转换，该提议重点关注信号处理中可能涉及的四类突触和/或突触外因素：（1）影响给定末端的毛细胞递质表型，包括多种毛细胞递质表型和突触后受体分布在给定末端相互作用的可能性，(2) 电位花萼和毛细胞之间的反馈，包括从毛细胞释放的递质到毛细胞本身的反馈，（3）递质释放的速率和随后的突触电流动态，由特定的突触前和突触后离子电流控制突触，以及（4）传入树突的综合特性，了解传入终端执行的信号处理的复杂性是开发前庭疾病治疗方法的必要步骤。一旦更彻底地理解了影响传入动力学的精确机制，就可以开发出适当且特定的药物来减少传入神经活动的异常爆发，从而减轻诸如 M 等疾病的眩晕症状的严重程度。 ¿尼科雷氏综合症。