Synaptic Determinants of Vestibular Afferent Dynamics

前庭传入动力学的突触决定因素

基本信息

批准号：
7850267
负责人：
Stephen Morris Highstein
金额：
$ 27.88万
依托单位：
MARINE BIOLOGICAL LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-17 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7850267
关键词：
Auditory 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 Glutamate Receptor Glutamates Goals Hair Hair Cells Hearing Immunofluorescence Immunologic In Situ Individual Investigation Ions Kinetics Labyrinth Light Location Maps Measures Mechanics Meniere&apos s Disease 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 public health relevance receptor relating to nervous system response sensor transmission process voltage voltage clamp

项目摘要

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. PUBLIC HEALTH RELEVANCE The inner ear contains the organs of hearing, balance and equilibrium. We study synaptic communication by chemical transmitter between hair cells (the primary mechanical sensors) and their innervated nerve fibers. Results from these investigations are expected to support the development of targeted therapies for peripheral vestibular disorders such as M¿ni¿re's syndrome and benign paroxysmal positional vertigo.

描述（由申请人证明）：在前庭系统中，在听觉和视觉系统中，在我们的研究中陷入了前进，并且其他人清楚地表明了从运河生物力学的偏离的传入响应在毛细胞上的发射器和受体表型和themint termint Termint Termint Termint Termint端子形成的处理实体，将毛细胞电位转化为CH中的频率代码。我们的传入：（1）毛状细胞发射机表型（s）影响给定的结尾，包括在给定的末端L上相互作用的多种毛细胞发射机表型和突触后分布的可能性在特定突触处，由突触前的电流控制的Celllf突触电流动力学，（4）传入的树突的复杂性更彻底地理解了异常的神经活动，从而缓解了诸如M¿的疾病中垂直症状的严重程度尼RE综合征。尼RE综合征和良性阵发性位置眩晕。