Circuit mechanisms of sound processing and detection in the auditory pathway

 说明书(申请人提供)：听觉通路中神经元反应的一个几乎普遍且重要的特性是对刺激的适应，使得神经元对相同声音的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(SSA)，当同一音调被频繁呈现时，神经元对该音调的反应比很少呈现该音调时更弱。SSA与早期在听觉通路中发现的适应从根本上不同，因为它不能概括到神经元的所有输入，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的机制还不是很清楚。在具体目标1中，我们检验了两种类型的抑制性中间神经元以互补的方式促进听觉皮质SSA的假设。在特定的目标2中，我们测试了听觉皮质向听觉中脑提供SSA的假设。了解引起SSA的机制很重要，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和异常声音检测之间的直接联系尚未建立。在特定的目标3中，我们测试了中枢听觉通路中的SSA有助于检测异常声音的假设。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的神经元机制；(2)分离不同的皮质抑制回路和皮质-丘脑反馈在听觉加工中的功能作用；(3)提供对这些回路元件在听觉感知中的直接测试。

 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.