Circuit mechanisms of sound processing and detection in the auditory pathway

 描述（由申请人提供）：听觉通路中神经元反应的一个几乎普遍和重要的性质是对刺激的适应，使得对相同声音的神经元反应取决于声音呈现的背景。在中枢听觉通路中，神经元表现出刺激特异性适应（stimulus-specific adaptation，SSA），即对同一个音调的反应，当音调出现频率较高时比音调出现频率较低时弱。SSA与早期在听觉通路中发现的适应性有着根本的不同，因为它不会在神经元的所有输入中泛化，因此不能用神经元兴奋性的普遍降低来解释。在听觉通路中引起SSA的机制还不清楚。在具体的目标1，我们测试的假设，两种类型的抑制性中间神经元促进SSA在听觉皮层中的互补的方式。在具体目标2中，我们检验了听觉皮层向听觉中脑提供SSA的假设。理解引起SSA的机制是很重要的，因为SSA与异常声音的检测有关，这是一个有助于声源分离和对象分组的过程。然而，SSA和异常声音的检测之间的直接联系尚未建立。在具体的目标3中，我们测试的假设，SSA在中央听觉通路促进检测异常的声音。影响：通过创新的光遗传学，电生理学和行为学方法，拟议的研究将（1）确定促进听觉通路适应的新神经元机制;（2）分离听觉处理中不同皮层抑制回路和皮质丘反馈的功能作用;（3）提供听觉感知中这些回路元件的直接测试。

 DESCRIPTION (provided by applicant): A nearly universal and important property of neuronal responses in the auditory pathway is adaptation to the stimulus, such that the neuronal responses to the same sound depend on the context in which the sound is presented. In central auditory pathway, neurons exhibit stimulus-specific adaptation (SSA), responding to the same tone more weakly when the tone is presented frequently, than when the tone is presented rarely. SSA is fundamentally different from adaptation found earlier in the auditory pathway, because it does not generalize across all inputs to a neuron, and therefore cannot be explained by a generalized reduction in excitability of the neuron. The mechanisms that give rise to SSA in the auditory pathway are not well understood. In specific aim 1, we test the hypothesis that two types of inhibitory interneurons facilitate SSA in the auditory cortex in a complementary fashion. In specific aim 2, we test the hypothesis that the auditory cortex provides SSA to the auditory midbrain. Understanding the mechanisms that give rise to SSA is important because SSA have been linked to detection of deviant sounds, a process that contributes to sound source separation and object grouping. However, a direct link between SSA and detection of deviant sounds has not been established. In specific aim 3, we test the hypothesis that SSA in the central auditory pathway facilitates detection of deviant sounds. Impact: Through innovative optogenetic, electrophysiological, and behavioral methods, the proposed research will (1) identify novel neuronal mechanisms that facilitate adaptation in the auditory pathway; (2) dissociate the functional roles of distinct cortical inhibitory circuits and cortico-collicular feeback in auditory processing; and (3) provide a direct test of these circuit elements in auditory perception.