Synaptic mechanisms in the auditory system

项目摘要 神经处理的早期阶段是由后期阶段提供信息的，这种下行控制起着多重作用， 重要角色。在感觉系统中，听觉系统的下行控制可能是最复杂的， 因此也是最不被理解的橄榄耳蜗传出系统是一种反射通路， 柯替氏器对声音信号的反应。在这里，我们重点关注内侧橄榄耳蜗系统（MOC）， 其通过复杂的胆碱能机制保护免受声学损伤并增强 耳蜗在噪声中检测信号的能力。MOC细胞接受来自耳蜗的神经反射输入 也有来自皮层和中脑的下行输入。此外，由乙酰胆碱兴奋的MOC神经元 受体激动剂提示局部胆碱能影响。这些不同的输入如何相对于一个 另一个是未知的。事实上，文献没有澄清这些输入的功能差异，因为 在经典的生理学或解剖学方法中独立地激活不同的神经元的局限性 MOC神经元的通路。在这里，我们建议使用现代小鼠遗传学和光遗传学技术， 结合脑切片系统中的电生理学，以确定 是橄榄耳蜗功能的基础主运行中心系统的另一个控制点是通过主运行中心抵押品 耳蜗核中，最终反馈到MOC细胞。如何从MOC胆碱能信号和 从中脑脚桥被盖控制的MOC是未知的。一个工作假设是， 和PPT作用于耳蜗核中不同的微电路，这转化为差分反馈控制 通过IC发送到MOC。这将在这里使用胆碱能神经元的电生理学和光遗传学分析进行测试。 影响耳蜗核在体外和体内。因为主运行中心系统在 保护免受噪音损害，很可能，这项研究的结果将导致一个更好的手段，以防止 或恢复人类听力。

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.