In-Vivo Patch Clamp Study of Auditory Midbrain

描述（由申请人提供）：本提案中的研究将使用体内全细胞记录来确定在下丘（IC）中形成EI细胞的各种回路，以及这些回路的功能影响。我们在以前的细胞外研究中表明，EI细胞 由于在IC群体中产生相同EI属性的各种电路，因此包括不同的组[4，10 - 12，18]。我们最近使用全细胞记录来确认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音诱发的突触后电位（PSP）中观察到[25]。在大多数EI细胞中，声音诱发的PSP模式显示出意想不到的预测，因为细胞外记录没有提示它们的存在。在一项初步研究中，我们还以一种新的方式评估了电路，通过计算单耳和双耳反应的兴奋性和抑制性电导。这种电路更令人惊讶，因为额外的输入被揭示出来，即使从声音诱发的PSP也不明显。一个意想不到的输入来自外侧丘系背核（DNLL）。DNLL是特殊的，因为它的细胞表达同侧诱发抑制的独特模式，并且它为IC提供强抑制性神经支配，这可能对IC对动态IID的反应产生深远影响[12，25]。PSP和电导揭示的电路表明，大多数EI细胞应选择性地响应动态双耳信号与IID随时间变化。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所暗示的令人兴奋的响应特征，促使了这项提议的研究。这些研究将通过记录尖峰、突触后电位（PSP）和计算产生每种反应的兴奋性和抑制性电导来确定在每种类型的EI细胞中引起单耳和双耳反应的输入。从电导导出的电路显示了每种EI类型如何以及为什么对一次呈现一个IID（静态IID）的两个IID做出响应，并建议每种EI类型应该如何响应随时间变化的动态IID，例如移动声源或从不同空间区域发出的多个声音。然后将用这些动态双耳刺激测试细胞，并将响应与从电导导出的电路预测的响应进行比较。此外，将进行简单的测试，以了解每个细胞是否从一个或两个DNLL接收输入。这些信息将深入了解听觉系统如何在复杂的声学环境中处理双耳信息，包括如何处理空间中的多个声源。这些信息可以被转化为算法，这些算法可能在机器人技术和/或为听力受损者制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.