In-Vivo Patch Clamp Study of Auditory Midbrain

描述(申请人提供)：这项建议中的研究将使用活体全细胞记录来确定在下丘(IC)形成EI细胞的各种电路，以及这些电路的功能影响。我们在之前的细胞外研究中表明，EI细胞 包括不同的组，这是由于在IC群体[4，10-12，18]中产生相同EI属性的不同电路。我们最近使用全细胞录音来证实，在我们之前的细胞外研究中提出的各种单耳和双耳输入可以在声诱发突触后电位(PSPs)中观察到[25]。在大多数EI细胞中，声音诱发的PSP的模式显示出意想不到的投射，因为细胞外录音没有给出它们存在的暗示。在一项初步研究中，我们还以一种新的方式评估了电路，通过计算作为单耳和双耳反应基础的兴奋性和抑制性电导。这一电路甚至更令人惊讶，因为发现了即使从声音诱发的PSP也不明显的额外输入。其中一个意想不到的输入来自外侧丘脑背核(DNLL)。DNLL是特殊的，因为它的细胞表达一种独特的同侧诱发抑制模式，它为IC提供了强大的抑制性神经，这可以对IC对动态IID的反应产生深远的影响[12，25]。PSP和电导揭示的电路表明，大多数EI细胞应该选择性地对动态双耳信号做出反应，其IID随着时间的推移而变化。正是这些令人惊讶的结果，特别是电导揭示的意想不到的电路和它们提出的令人兴奋的响应特征，促使了这项提议中的研究。这些研究将通过记录棘波、突触后电位(PSP)以及计算产生每种反应的兴奋性和抑制性电导来识别在每种类型的EI细胞中引起单耳和双耳反应的输入。从电导得出的电路显示了每种EI类型如何以及为什么一次一个地响应两个IID(静态IID)，并建议每种EI类型应该如何响应随时间变化的动态IID，例如移动的声源或从不同空间区域发出的多种声音。然后用这些动态双耳刺激对电池进行测试，并将反应与从电导得出的电路预测的反应进行比较。此外，还将进行简单的测试，以深入了解每个细胞是否从一个或两个DNLL接收输入。这些信息将提供有关听觉系统如何在复杂的声学环境中处理双耳信息的见解，包括它如何处理空间中的多个声源。这些信息可以被翻译成算法，这些算法可能会在机器人学和/或为听力受损的人建造助听器方面证明是有用的。

DESCRIPTION (provided by applicant): The studies in this proposal will use in vivo whole cell recordings to determine the various circuits that form EI cells in the inferior colliculus (IC), an the functional impacts of those circuits. We showed in previous extracellular studies that EI cells comprise a diverse group due to the various circuits that generate the same EI property among the IC population [4,10-12,18]. We recently used whole cell recordings to confirm that the various monaural and binaural inputs proposed in our previous extracellular studies could be observed in the sound evoked post-synaptic potentials (PSPs) [25]. In most EI cells, the patterns of sound evoked PSPs showed projections that were unexpected, since extracellular recordings gave no hint of their presence. In a pilot study we also evaluated the circuitry in a new way, by computing the excitatory and inhibitory conductances that underlie monaural and binaural responses. That circuitry was even more surprising since additional inputs were revealed that were not apparent even from the sound evoked PSPs. One of the unexpected inputs is from the dorsal nucleus of the lateral lemniscus (DNLL). The DNLL is special because its cells express a unique pattern of ipsilateral evoked inhibition and it provides a strong inhibitory innervation to the IC, which can have profound influences on IC responses to dynamic IIDs [12, 25]. The circuitry revealed by both PSPs and conductances suggests that most EI cells should respond selectively to dynamic binaural signals with IIDs that change over time. It was these surprising results, especially the unexpected circuitry revealed by conductances and the exciting response features they suggest, that prompt the studies in this proposal. The studies will identify the inputs that evoke both monaural and binaural responses in each type of EI cell by recording spikes, postsynaptic potentials (PSPs) and by computing the excitatory and inhibitory conductances that generate each response. The circuits derived from the conductances show how and why each EI type responds to both IIDs presented one at a time (static IIDs) and suggest how each EI type should respond to dynamic IIDs that change over time, such as moving sound sources or multiple sounds that emanate from different regions of space. The cells will then be tested with those dynamic binaural stimuli and the responses will be compared to the responses predicted from the circuitry derived from conductances. In addition, simple tests will be administered that provide insights into whether or not each cell receives inputs from one or both DNLLs. This information will provide insights into how the auditory system handles binaural information in complex acoustic environments, including how it deals with multiple sound sources in space. Such information could be translated into algorithms that might prove useful in robotics and/or in the construction of hearing aids for the hearing impaired.