In-Vivo Patch Clamp Studies of the Auditory Midbrain

描述(申请人提供)：下丘(IC)是听觉系统中的一个神经节，因为它处理和整合几乎所有来自较低中枢的上升声信息，从而决定什么形式的信息被传达到前脑的较高区域。与投射的大收敛一致，IC神经元的反应特性高度不同。这种多样性是由于支配每个神经元的输入的特殊补充以及它们的固有离子通道。抑制是特别重要的，因为抑制在更广泛的兴奋性神经支配的背景下塑造了广泛的紧急反应特性。由于细胞外记录不能直接看到抑制，我将使用来自IC神经元的活体全细胞记录来获得更直接和更详细的声音诱发抑制的视图，并生成关于IC神经元的反应特性、它们处理声学信息的机制及其形态特征的独特和更全面的图像。反应特征包括它们的内在特性，通过对注入的电流步骤的反应来揭示，它们的音调诱发的突触反应和特别注意声音诱发的抑制的放电的调节，它们对自然交流呼叫的反应，以及它们对向上或向下FM扫描的定向偏好。这些实验的独特之处在于，这一系列反应特征从未在单个IC细胞中被记录下来，它们将被用来评估内在通道如何与配体门控事件相互作用，以塑造IC细胞的反应特性。建议的研究集中于抑制的作用，抑制在IC中对一些病理条件和听力损伤是重要的。抑制的作用可能与老年人言语知觉的下降特别相关，这与听觉系统中GABA能神经元的年龄相关性丢失有关。由于拟议的研究将评估抑制在处理交流电话中的作用，它们可能为语音处理提供见解，从而解释为什么老年人经常经历言语感知能力的下降。

DESCRIPTION (provided by applicant): The inferior colliculus (IC) is a nexus in the auditory system since it processes and integrates almost all ascending acoustic information from lower centers and thereby determines what form of information is conveyed to higher regions in the forebrain. Consistent with the large convergence of projections, the response properties of IC neurons are highly diverse. The diversity is due to the particular complement of inputs that innervate each neuron and to their intrinsic ion channels. Inhibition is particularly important, because inhibition sculpts a wide range of emergent response properties from the backdrop of more expansive and less specific excitatory innervation. Because inhibition cannot be directly seen with extracellular recordings, I will use in vivo whole cell recordings from IC neurons to obtain a more direct and detailed view of sound evoked inhibition, and generate a unique and more comprehensive picture of the response properties of IC neurons, the mechanisms with which they process acoustic information and their morphologic features. The response features include their intrinsic properties, revealed by responses to injected current steps, the tuning of their tone evoked synaptic responses and discharges with particular attention directed at sound evoked inhibition, their responses to natural communication calls, and their directional preferences for upward or downward FM sweeps. What makes these experiments unique is that this constellation of response features has never been recorded in individual IC cells, and they will be used to evaluate how intrinsic channels interact with ligand-gated events to shape the response properties in IC cells. The proposed studies focus on the roles of inhibition, and inhibition in the IC is important for a number of pathological conditions and hearing impairments. The roles of inhibition may be especially relevant for the decline of speech perception in the elderly, which is correlated with age related loss of GABAergic neurons in the auditory system. Since the proposed studies will evaluate the role of inhibition in the processing of communication calls, they may provide insights into the processing of speech, and hence into why the elderly often experience a decline in speech perception.