Dendritic integration and synaptic plasticity in the MSO

描述（由申请人提供）：声音的快速、时变特征对于人类和其他哺乳动物定位声源以及解释语音和通信呼叫是必不可少的。这项研究的广泛目标是了解这些特征在大脑中是如何处理的，以及了解听觉回路中的神经元如何在发育过程中获得适当的生物物理特性来执行这些计算。该建议的重点是内侧上级橄榄（MSO），第一个和关键的阶段，用于处理两耳的耳间时间差（ITD），线索，用于本地化的声音沿着水平面。在MSO中，ITD通过符合检测过程计算和传送，通过该过程，来自双耳的兴奋性输入被分离到双极树突状乔木的不同分支上，并以亚毫秒的时间分辨率在索马求和。因此，要理解声音定位线索在MSO中是如何处理的，就需要了解突触输入的时间和强度在两组树突中是如何控制的。这项建议将调查的假设，即在MSO神经元的快速时间处理能力的发展不是预先编程，但在听力发作后，由突触和放电活动驱动。我们将结合树突状斑块记录，双光子和宽场钙成像和解剖技术来探讨这一假设。目的1将研究轴突初始段在发育过程中形成放电特征的特征和作用。目标2将研究突触活动如何通过超极化激活的阳离子通道的变化转化为内在神经元精度的增加，目标3将揭示兴奋性突触强度沿着MSO树突的空间模式，以及这种模式是否在早期听觉体验过程中发生改变。这些实验的信息不仅对理解哺乳动物听力的基本机制很重要，而且对理解正常听觉发育的改变（例如通过听力缺陷或耳聋）如何塑造听觉回路的功能以及这些回路如何通过听觉假体对听觉活动的重新引入做出反应也很重要。

DESCRIPTION (provided by applicant: Fast, time-varying features of sound are essential for humans and other mammals for localizing sound sources as well interpreting speech and communication calls. The broad goal of this research is both to understand how these features are processed in the brain, as well as to understand how neurons in auditory circuits acquire the appropriate biophysical properties during development to carry out these computations. 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 localizing sounds along the horizontal plane. In the MSO, ITDs are computed and conveyed through the process of coincidence detection, by which excitatory inputs from the two ears are segregated onto different branches of a bipolar dendritic arbor and sum at the soma with submillisecond time resolution. Thus an understanding of how sound localization cues are processed in the MSO in turn requires knowledge of how the timing and strength of synaptic inputs are controlled in the two sets of dendrites. This proposal will investigate the hypothesis that the development of fast time-processing capabilities in MSO neurons is not preprogrammed, but is driven after hearing onset by synaptic and firing activity. We will explore this hypothesis by combining dendritic patch recordings, 2-photon and wide-field calcium imaging and anatomical techniques. Aim 1 will examine the characteristics and role of the axon initial segment in shaping firing characteristics during development. Aim 2 will examine how synaptic activity is translated into increasing intrinsic neuronal precision, via changes in hyperpolarization-activated cation channels, and Aim 3 will reveal the spatial pattern of excitatory synapse strength along MSO dendrites and whether this pattern is altered during the course of early auditory experience. The information from these experiments is important not only for understanding basic mechanisms of mammalian hearing but also for understanding how alterations of normal auditory development (e.g. via hearing deficits or deafness) shape the function of auditory circuits and how these circuits respond to the reintroduction of auditory activity via auditory prostheses.