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纽带，因为它处理和整合几乎所有来自较低中心的上升声信息，从而决定什么形式的信息被传递到前脑的较高区域。与投影的大收敛性一致，IC神经元的响应特性具有高度的多样性。这种多样性是由于支配每个神经元的输入的特定补充以及它们固有的离子通道。抑制是特别重要的，因为抑制在更广泛和更少特异性的兴奋性神经支配的背景下塑造了广泛的紧急反应特性。由于抑制不能通过细胞外记录直接看到，我将使用来自IC神经元的体内全细胞记录来获得更直接和详细的声音诱发抑制视图，并生成IC神经元响应特性的独特和更全面的图像，它们处理声音信息的机制及其形态特征。反应特征包括它们的内在特性，通过对注入电流步骤的反应揭示，它们的音调调谐引起突触反应，特别注意声音引起的放电引起抑制，它们对自然交流呼叫的反应，以及它们对向上或向下FM扫描的方向偏好。这些实验的独特之处在于，这些响应特征的组合从未在单个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，从而形成IC细胞的响应特性。提出的研究重点是抑制的作用，IC的抑制对许多病理条件和听力障碍都很重要。抑制的作用可能与老年人的语言感知能力下降特别相关，这与听觉系统中gaba能神经元的年龄相关损失有关。由于拟议的研究将评估抑制在通信呼叫处理中的作用，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语音感知下降。

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.