Cholinergic Modulation of Cochlear Plasticity

这项研究方案考察了声音创伤、发育和衰老对 耳蜗毛细胞的神经支配，特别关注传出系统的作用。 新出现的证据表明传入和传出突触以一种未知的方式相互作用 在发育关键期，并伴随着声学功能的改变。怎么可能？ 这样的互动会发生吗？是毛细胞的活动决定了突触的排列，还是 突触“争夺”地盘？特别是，传出输入是否在 毛细胞功能分化？或者，传出(和传入)突触依赖于 毛细胞兴奋的变化？为了解决这些问题，毛细胞的兴奋性和突触 将详细介绍AChR缺失(α9缺失)小鼠在听觉创伤前后的功能，以及 功能AChRs增强型(α9L9‘T)。听觉功能和突触功能将是 在α9 Null和α9L9‘T小鼠的衰老动物中进行评估。最后，人的发育成熟 将在TMC2机械转导缺失的小鼠中检测IHC上的突触。

This research proposal examines the impact of acoustic trauma, development and aging on the innervation of cochlear hair cells, with particular focus on the role of the efferent system. Emerging evidence suggests that afferent and efferent synapses interact in undefined ways during a developmental critical period, and in parallel with altered acoustic function. How might such interactions occur? Does activity of the hair cell determine synaptic arrangements, or do synapses ‘compete’ for territory? In particular, do efferent inputs play an instructive role in the differentiation of hair cell function? Or, are efferent (and afferent) synapses dependent upon changes in hair cell excitation? To approach these questions, hair cell excitability and synaptic function will be detailed before and after acoustic trauma in AChR-null (α9 null) mice, and in those with gain of function AChRs (α9L9’T). Auditory function and synaptopathy will be assessed in aging animals in α9 null and α9L9’T mice. Finally, the developmental maturation of synapses on IHCs will be examined in TMC2 mechanotransduction null mice.