Mechanism of Plasticity in an Auditory Brainstem Nucleus

描述(申请人提供)：这项工作的目标是研究调节外侧上橄榄(LSO)突触发育和细化的生理机制。LSO是一种双耳听性脑干核团，其主神经元接受来自不同核源的兴奋和抑制。在成熟的啮齿动物中，LSO的兴奋性和抑制性传入在音调上组织和频率匹配，遵循功能和解剖学上的完善程序。这些独特的条件使LSO成为研究兴奋性和抑制性可塑性机制如何协调以产生适当平衡的神经回路的模型系统。这个建议建立在我们的初步工作的基础上，证明了超极化对于LSO中兴奋性突触的长期增强的显著和意想不到的必要性，并概述了一系列实验来测试调节这种新形式可塑性的机制。 与公共卫生相关：这个项目的目标是深入了解哺乳动物听觉系统中形成精确神经元连接的细胞机制。研究这些机制将有助于更好地理解听觉处理障碍的原因和潜在的治疗方法，如发育性阅读障碍、语音处理障碍和自闭症。

DESCRIPTION (provided by applicant): The goal of this work is to investigate physiological mechanisms mediating the development and refinement of synapses in the lateral superior olive (LSO). The LSO is a binaural auditory brainstem nucleus whose principal neurons receive excitation and inhibition from distinct nuclear sources. Following a developmental program of functional and anatomical synaptic refinement, excitatory and inhibitory afferents to the LSO are tonotopically organized and frequency matched in the mature rodent. These unique conditions make the LSO a model system for studying how mechanisms of excitatory and inhibitory plasticity may be coordinated to produce appropriately balanced neural circuits. This proposal builds on our preliminary work demonstrating the striking and unexpected necessity of hyperpolarization for long-term potentiation of excitatory synapses in the LSO, and outlines a series of experiments to test mechanisms mediating this novel form of plasticity. PUBLIC HEALTH RELEVANCE: This goal of this project is to provide insight into the cellular mechanisms underlying the formation of precise neuronal connections in the mammalian auditory system. Studying these mechanisms will lead to a better understanding of causes and potential treatments of auditory processing disorders such as developmental dyslexia, speech processing impairments, and autism.