Auditory Neural Filters Studied with in vivo Whole-Cell Recordings.

描述(申请人提供)：这项研究的广泛目标是了解神经过滤器是如何形成的，即神经元如何对某些刺激做出反应，而不是对其他刺激？许多听觉过滤器被认为是在下丘(1C)形成的，包括对频率调制(FM)方向的反应选择性，其中一个细胞可能对FM的首选方向有强烈的反应，但对非FM没有反应。以往对调频方向选择性的研究大多使用细胞外电极记录棘波，然后使用棘波计数来推断调频方向选择性的机制，包括突触输入模式和细胞的固有特性。我将使用全细胞膜片钳技术直接测量声诱发突触后电位(PSP)和棘波，以及基本的生物物理特性，如输入电阻和细胞电容。我还将使用PSP数据来计算声音诱发的突触电导的时间和大小，包括抑制和兴奋的不同值。这些直接测量将使我能够以比细胞外电极更全面的方式评估1C中FM方向选择性背后的机制。有三个主要目标。首先，我将在细胞内描述1C神经元对FM方向的选择性程度，包括FM的速度和强度。其次，我将确定是否以及在多大程度上FM方向选择性是在1C中从头产生的，还是从突触输入继承的，在突触输入中，传入神经元本身具有方向选择性。这将包括对激发和/或抑制的光谱-时间不对称性在多大程度上造成方向选择性的分析。最后，我将比较PSP中存在的方向选择性与尖峰计数中的方向选择性，以确定尖峰阈值是否以及在多大程度上提高方向选择性。听力损失的主要治疗方法包括人工耳蜗和助听器。任何区分生物相关声音和背景噪音的电路都可能对这两种治疗方法都有利。由于功能模块是语音的重要组成部分，了解哺乳动物大脑是如何处理功能模块的，可能有助于提高助听器和人工耳蜗在嘈杂环境中区分语音的程度。

DESCRIPTION (provided by applicant): The broad objective of this research is to understand how neural filters are formed, i.e. how do neurons respond to certain stimuli, but not to others? Many auditory filters are believed to be formed in the inferior colliculus (1C), including the response selectivity for the direction of frequency modulation (FM), where a cell may respond strongly to the preferred direction of FM, but not to the non-preferred FM. In the past, most studies on FM direction selectivity used extracellular electrodes to record spikes, and then used the spike counts to infer the mechanisms underlying FM direction selectivity, including patterns of synaptic input and the cell's intrinsic properties. I will use the whole-cell patch-clamp technique to directly measure sound- evoked post-synaptic potentials (PSPs) and spikes, as well as basic biophysical properties such as input resistance and cell capacitance. I will also use the PSP data to calculate the timing and magnitudes of the sound-evoked synaptic conductances, including separate values for inhibition and excitation. These direct measurements will enable me to evaluate the mechanisms underlying FM direction selectivity in the 1C in a more comprehensive manner than possible with extracellular electrodes. There are three major goals. First, I will characterize intracellularly the extent to which 1C neurons are selective for the direction of FM, including the rate and intensity of the FMs. Second, I will determine whether and to what extent FM direction selectivity is created de novo in the 1C, or is inherited from the synaptic inputs, where the afferent neurons are themselves directionally selective. This will include an analysis of the extent to which direction selectivity is created by spectral-temporal asymmetries of excitation and/ or inhibition. Finally, I will compare the direction selectivity that is present in the PSPs to the direction selectivity in the spike counts to determine whether and to what extent spike threshold enhances direction selectivity. The major treatments for hearing loss include cochlear implants and hearing aids. Any circuit that distinguishes biologically relevant sounds from background noise could benefit both treatments. Because FMs are an important component of speech, understanding how mammalian brains process FMs may help to improve the degree to which hearing aids and cochlear implants can distinguish speech sounds in noisy environments.