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连接点，因为它处理和整合几乎所有来自较低中心的上行声学信息，从而确定将何种形式的信息传递到前脑中的较高区域。与投影的大收敛性一致，IC神经元的响应特性是高度多样的。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的内在离子通道。抑制作用尤为重要，因为抑制作用在更广泛、更不具体的兴奋性神经支配的背景下塑造了广泛的应急反应特性。由于抑制不能直接看到细胞外的录音，我将使用在体内的整个细胞录音IC神经元获得更直接和详细的声音诱发抑制的看法，并产生一个独特的和更全面的图片IC神经元的响应特性，与它们的机制，它们处理声学信息和它们的形态特征。响应特征包括它们的内在特性，通过对注入电流阶跃的响应、它们的音调诱发的突触响应的调谐和特别注意针对声音诱发的抑制的放电、它们对自然通信呼叫的响应以及它们对向上或向下FM扫描的方向偏好来揭示。这些实验的独特之处在于，这种反应特征的星座从未在单个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。拟议的研究集中在抑制的作用，抑制在IC是重要的一些病理条件和听力障碍。抑制的作用可能与老年人的言语知觉下降特别相关，这与听觉系统中与年龄相关的GABA能神经元的损失有关。由于拟议的研究将评估抑制在处理通信呼叫中的作用，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经常会出现语音感知下降。

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.