Dendritic Integration and Synaptic Plasticity in the MSO

项目摘要 人类和其他哺乳动物使用声音中的时间精细结构来识别和帮助 在三维空间中定位听觉对象。这项研究的主要目标是 了解声音定位线索是如何在大脑中处理的，以及了解如何 在发育过程中，底层回路中的神经元获得适当的生物物理特性。 该建议侧重于内侧上级橄榄（MSO），这是加工的第一个关键阶段 来自两耳的耳间时间差（ITD），用于水平声音定位的线索 以及用于理解噪声环境中的语音模式。ITD在MSO中通过 重合检测的过程，其中来自两个兴奋性输入的同时到达 通过动作电位放电检测和传送耳朵，时间分辨率为几十秒。 微秒。 MSO的神经元在历史上一直被认为是功能和形态 同质的然而，我们的初步数据驳斥了这种简单的MSO观点：我们假设 相反，枝晶形态和电性能变化决定性地形成了 空间感受野，并且这些差异在听力开始后部分受到水平的影响。 和神经活动模式我们将通过结合成对的树突和体细胞来解决这些问题。 斑片记录，房室模型，光敏通道的图案化LED照明 阻断剂和听力操纵。目标1将讨论新的 发现了在体外使用贴片，MSO神经元的电生理特性的tonotopic多样性， 钳夹记录。目标2将扩展这些分析，以了解MSO中的功能多样性 神经元中的电压门控通道的表达水平和性质的差异赋予了神经元 轴突起始段。目标3将探讨树突状结构本身的多样性如何塑造 双耳重合的最佳检测的时间要求。 从这些实验中获得的信息将增加我们对机制的理解 哺乳动物潜在的空间听觉，以及控制空间听觉的发育过程。 在MSO中形成关键电路元件。由于双耳听力对说话很重要， 儿童的感知和语言习得，对双耳电路功能的机械理解 和发展可能最终为解决听力障碍的临床策略提供信息。

Project Summary Humans and other mammals use the temporal fine structure in sounds to identify and help localize auditory objects in three-dimensional space. The broad goal of this research is both to understand how sound localization cues are processed in the brain as well as to understand how neurons in the underlying circuitry acquire the appropriate biophysical properties during development. This proposal focuses on the medial superior olive (MSO), the first and critical stage for processing interaural time differences (ITDs) from the two ears, cues that are used for horizontal sound localization as well as for understanding speech patterns in noisy environments. ITDs are computed in the MSO via the process of coincidence detection, in which the simultaneous arrival of excitatory inputs from the two ears is detected and conveyed through action potential firing with a time resolution of a few tens of microseconds. The neurons of the MSO have historically been assumed to be functionally and morphologically homogeneous. However, our preliminary data refutes this simplistic view of the MSO: we hypothesize instead that variation in dendritic morphology and electrical properties critically shapes the location of spatial receptive fields, and that these differences are in part influenced after hearing onset by the level and pattern of neural activity. We will address these questions by combining paired dendritic and somatic patch recordings, compartmental modeling, patterned LED illumination of light-sensitive channel blockers, and hearing manipulations. Aim 1 will address the functional significance of the newly discovered tonotopic diversity in electophysiological properties of MSO neurons both in vitro using patch- clamp recordings. Aim 2 will extend these analyses to understand how the functional diversity in MSO neurons is conferred by differences in the expression levels and properties of voltage-gated channels in the axon initial segment. Aim 3 will explore how the diversity of dendritic structure itself shapes the temporal requirements for optimal detection of binaural coincidence. The information from these experiments will increase our understanding of the mechanisms underlying spatial hearing in mammals, as well as the developmental processes that control the formation of a critical circuit component in the MSO. As binaural hearing is important for speech perception and language acquisition in children, a mechanistic understanding of binaural circuit function and development may ultimately inform clinical strategies for addressing hearing impairments.