Synaptic mechanisms in the auditory system

听觉系统中的突触机制

基本信息

批准号：
10187785
负责人：
LAURENCE O TRUSSELL
金额：
$ 6.38万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10187785
关键词：
Acetylcholine Acoustic Nerve Acoustics Affect Anatomy Auditory area Auditory system Axon Back Biophysical Process Brain Brain Stem Cell Nucleus Cells Cholinergic Fibers Closure by clamp Cochlea Cochlear nucleus Complex Contralateral Development Ear Efferent Pathways Electrophysiology (science)Environment Feedback Feeds Genetic Glutamates Hearing Human In Vitro Inferior Colliculus Injections Ipsilateral Kinetics Light Literature Medial Methods Midbrain structure Modernization Mus Neural Pathways Neurons Noise Nuclear Organ of Corti Outer Hair Cells Output Pathway interactions Pattern Pedunculopontine Tegmental Nucleus Physiological Play Population Property Reflex action Resolution Role Shapes Signal Transduction Site Slice Source Stimulus Synapses Synaptic Membranes System Techniques Testing Transgenic Mice Translating Viral acetylcholine receptor agonist brain circuitry cell type cholinergic cholinergic neuron extracellular hearing impairment in vivo mouse genetics neural circuit optogenetics prevent recruit relating to nervous system response sensory system stellate cell transmission process trapezoid body

项目摘要

Project Summary Early stages of neural processing are informed by later stages, and this descending control plays multiple, important roles. Among sensory systems, descending control in the auditory system is probably most complex, and therefore least understood. The olivocochlear efferent system is a reflex pathway that modifies the response of the organ of Corti to acoustic signals. Here we focus on the medial olivocochlear system (MOC), which through a sophisticated cholinergic mechanism protects against acoustic damage and enhances the ability of the cochlea to detect signals in noise. MOC cells receive glutamatergic reflex input from cochlear nucleus but also descending input from cortex and midbrain. Moreover, MOC neurons excited by acetylcholine receptor agonists suggesting local cholinergic influences. How these distinct inputs function relative to one another is unknown. Indeed, the literature has not clarified functional differences in these inputs because of limitations in the classical physiological or anatomical approaches to independently activate different neural pathways to the MOC neurons. Here we propose to use modern mouse genetic and optogenetic techniques combined with electrophysiology in a brain slice system to determine the intrinsic and synaptic properties that underlie olivocochlear function. An additional point of control of MOC system is through MOC collaterals made in the cochlear nucleus, which ultimately feeds back to MOC cells. How cholinergic signaling from MOC and from midbrain pedunculopontine tegmental controls the MOC is unknown. A working hypothesis is that MOC and PPT act on distinct microcircuits in cochlear nucleus and that this translates to differential feedback control to MOC via the IC. This will be tested here using electrophysiological and optogenetic analysis of cholinergic influences in the cochlear nucleus in vitro and in vivo. Because the MOC system plays an essential in protection against noise damage, it is likely that the results of this study will lead to a better means to prevent damage to, or recover, human hearing.

项目概要神经处理的早期阶段是由后期阶段通知的，这种下行控制起着多重作用，重要的角色。在感觉系统中，听觉系统的下行控制可能是最复杂的，因此最不被理解。橄榄耳蜗传出系统是一种反射途径，可以改变柯蒂氏器对声音信号的反应。这里我们重点关注内侧橄榄耳蜗系统（MOC），它通过复杂的胆碱能机制防止声音损伤并增强耳蜗检测噪声中信号的能力。 MOC 细胞接收来自耳蜗的谷氨酸反射输入核也有来自皮层和中脑的下行输入。此外，MOC神经元被乙酰胆碱兴奋受体激动剂表明局部胆碱能影响。这些不同的输入如何相对于一个另一个未知。事实上，文献并没有阐明这些输入的功能差异，因为经典生理学或解剖学方法独立激活不同神经元的局限性 MOC 神经元的通路。在这里我们建议使用现代小鼠遗传和光遗传学技术与脑切片系统中的电生理学相结合，以确定其内在和突触特性橄榄耳蜗功能的基础。 MOC 系统的另一个控制点是通过 MOC 抵押品位于耳蜗核中，最终反馈给 MOC 细胞。 MOC 的胆碱能信号如何中脑脚桥被盖控制的 MOC 未知。一个可行的假设是 MOC 和 PPT 作用于耳蜗核中的不同微电路，这转化为差分反馈控制通过 IC 到 MOC。这将在这里使用胆碱能的电生理学和光遗传学分析进行测试体外和体内对耳蜗核的影响。因为 MOC 系统在防止噪音损害，这项研究的结果很可能会带来更好的方法来防止损害或恢复人类听力。