Cochlear Neurotransmitters

耳蜗神经递质

基本信息

批准号：
9124823
负责人：
WILLIAM F SEWELL
金额：
$ 34.85万
依托单位：
MASSACHUSETTS EYE AND EAR INFIRMARY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9124823
关键词：
AMPA Receptors Acoustic Nerve Acoustic Stimulation Acoustics Address Afferent Neurons Attenuated Auditory Auditory Physiology Biochemical Cochlea Code Complex Coupled Dendrites Excision Failure Fiber Figs - dietary Future Gene Deletion Glutamate Receptor Hair Cells Health Hearing Inner Hair Cells Kainic Acid Receptors Knockout Mice Knowledge Laboratories Lead Mediating Metabotropic Glutamate Receptors Methodology Monitor Mus N-Methyl-D-Aspartate Receptors N-Methylaspartate Natural regeneration Nervous system structure Neurons Neuropathy Neurotransmitters Normal Cell Pathology Pattern Pharmaceutical Preparations Physiological Play Predisposition Process Receptor Activation Receptor Gene Role Sensorineural Hearing Loss Sensory Signal Transduction Stimulus Synapses Synaptic Membranes Synaptic Transmission Testing Thinking Time Tinnitus Trauma Work auditory stimulus base desensitization excitotoxicity hearing impairment improved in vivo interest kainate nerve supply neurotransmitter release novel strategies receptor receptor recycling reinnervation response signal processing sound spiral ganglion synaptic function tool trafficking transmission process

项目摘要

DESCRIPTION (provided by applicant): We have known for decades that glutamate receptors mediate synaptic transmission between the inner hair cell and its afferent fiber, yet we know astonishingly little about the contributions of the different types of glutamate receptors to stimulus coding and auditory pathology. All 4 basic types of glutamate receptors (AMPA, kainate, metabotropic, and NMDA) are present on afferent terminals but the only one we really understand well is the AMPA receptor, which mediates moment-by-moment transmission at this synapse. Understanding how these different types of glutamate receptors interact to code acoustic signals will illuminate how this synapse achieves some of its extraordinary information transfer capabilities and how its failure modes can lead to excitotoxic hearing loss. The specific aims are: Aim 1: How do different glutamate receptors cooperate to produce sound-evoked responses in the cochlea? Aim 2. Test the hypothesis that kainate receptors are trafficked and regulated at the hair cell synapse. Aim 3: How do different glutamate receptors contribute to excitotoxicity in the cochlea? Understanding the roles of these receptors in cochlear function could also lead to strategies to improve hearing. For example, a greater understanding of the role NMDA receptors play in the cochlea could lead to new tinnitus therapies. Understanding trafficking could lead to drugs that improve hearing by increasing the sensitivity of afferent neurons to auditory stimuli. Knowledge of the roles that the different neurotransmitters play in cochlear function could help in developing strategies for reinnervating hair cells in future therapies based on regenerating hair cells. Finally, understanding the roles of these different glutamate receptors at the hair cell afferent synapse provides an extraordinary opportunity to understand fundamental issues of glutamate receptor coding with relevance to understanding synaptic function in the nervous system in general. The simplicity and extreme organization of the innervation pattern in the cochlea, coupled to the ability to precisely deliver sensory signals and monitor responses while perfusing the synapse with drugs allows us to precisely address the roles of these receptors in signal processing in vivo.

描述（由申请人提供）：我们已经知道数十年来，谷氨酸受体介导内毛细胞及其传入纤维之间的突触传播，但我们对不同类型的谷氨酸受体对刺激编码和听觉病理学的贡献知之甚少。所有4种基本类型的谷氨酸受体（AMPA，Kainate，Agotropic和NMDA）都存在于传入末端上，但我们真正理解的唯一一种是AMPA受体，AMPA受体在此突触中逐步传播。了解这些不同类型的谷氨酸受体如何与代码声信号相互作用将阐明该突触如何实现其某些非凡信息传输功能以及其失效模式如何导致兴奋性听力损失。具体目的是：目标1：不同的谷氨酸受体如何合作在耳蜗中产生诱发的反应？ AIM 2。检验海藻酸盐受体在毛细胞突触中被贩运和调节的假设。 AIM 3：不同的谷氨酸受体如何导致耳蜗兴奋性毒性？了解这些受体在人工耳蜗功能中的作用也可能导致改善听力的策略。例如，对NMDA受体在耳蜗中所起的作用有更多的了解可能导致新的耳鸣疗法。了解贩运可能会导致药物通过提高传入神经元对听觉刺激的敏感性来改善听力的药物。了解不同神经递质在人工耳蜗功能中发挥的作用可能有助于制定基于再生毛细胞在未来疗法中重新构造毛细胞的策略。最后，了解这些不同的谷氨酸受体在毛细胞传入突触中的作用提供了一个非同寻常的机会，可以理解谷氨酸受体编码的基本问题，与理解一般的神经系统中的突触功能有关。耳蜗中神经支配模式的简单性和极端组织，与精确传递感觉信号的能力相结合在用药物灌注突触的同时，监测反应使我们能够精确地解决这些受体在体内信号处理中的作用。