In-Vivo Patch Clamp Studies of the Auditory Midbrain

描述（由申请人提供）：下丘（IC）是听觉系统中的一个纽带，因为它处理和整合来自较低中心的几乎所有上行声音信息，从而确定什么形式的信息被传递到前脑的较高区域。与预测的大收敛一致，IC 神经元的反应特性是高度多样化的。这种多样性是由于支配每个神经元的输入的特定补充及其固有的离子通道造成的。抑制尤为重要，因为抑制在更广泛和不太具体的兴奋性神经支配的背景下塑造了广泛的紧急反应特性。由于细胞外记录无法直接观察到抑制作用，因此我将使用 IC 神经元的体内全细胞记录来获得声音诱发抑制的更直接和详细的视图，并生成 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且更全面的图像。响应特征包括它们的内在特性，通过对注入电流步骤的响应来揭示，它们的音调诱发突触反应和放电的调整，特别注意声音诱发的抑制，它们对自然通信呼叫的响应，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，这些反应特征从未在单个 IC 细胞中记录过，它们将用于评估内在通道如何与配体门控事件相互作用，以塑造 IC 细胞中的反应特性。拟议的研究重点是抑制的作用，IC 中的抑制对于许多病理状况和听力障碍很重要。抑制作用可能与老年人言语感知能力的下降尤其相关，这与听觉系统中与年龄相关的 GABA 能神经元的丧失有关。由于拟议的研究将评估抑制在通信呼叫处理中的作用，因此它们可能会提供对语音处理的见解，从而了解为什么老年人的言语感知能力经常下降。

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.