Cortical circuits for temporal integration of multi-frequency sounds

项目概要 在我们的日常生活中，即使面对多个声源，我们的大脑也会将频率成分结合在一起 属于同一来源并识别各个声音对象。在人类中，光谱分组 单个声音感知的分量依赖于其开始的精确同步（< 30 毫秒窗口） 时间，这种分组在我们对语言的感知中起着至关重要的作用。尽管这很重要 “感觉特征绑定”，我们对神经元回路机制仍然知之甚少。 大脑整合频谱和时间分布的声音输入。为了解决这一知识差距， 该项目将使用小鼠听觉皮层来定义谐波结合的神经元回路 一个模型系统。小鼠听觉皮层由五个区域组成，这些区域相互连接形成分层结构 处理流。我们的初步数据表明，较高的听觉皮层区域 A2 选择性地 代表具有一致开始时间的多频率声音。我们假设 A2 中的抑制电路 以同步依赖的方式对音调的整合进行门控，这种门控使小鼠能够检测 谐波声音。我们的目标是利用尖端的双光子技术来检验这一假设 可用于小鼠的钙成像和体内全细胞记录技术。为了实现我们的目标， 该项目旨在 (1) 确定跨听觉区域的独特频谱-时间整合（宏观 和细胞水平钙成像），（2）剖析光谱-时间整合的电路机制 （体内全细胞记录），以及（3）确定高级听觉皮层在处理过程中的感知作用 谐波（行为过程中的光遗传学）。简单小鼠皮层的发现应该提供第一步 最终理解实现口头交流的“特征绑定”电路，以及如何 他们在患病的大脑中失败。

PROJECT SUMMARY In our daily life, even in the face of multiple sound sources, our brain binds together frequency components that belong to the same source and recognizes individual sound objects. In humans, grouping of spectral components into single sound perception relies on the precise synchrony (< 30-ms window) of their onset timings, and this grouping plays a critical role in our perception of language. Despite the importance of this “sensory feature binding”, we still know little regarding the neuronal circuit mechanisms underlying how our brain integrates spectrally and temporally distributed sound inputs. To address this gap in knowledge, this project will define neuronal circuits underlying the binding of harmonic sounds using mouse auditory cortex as a model system. Mouse auditory cortex consists of five areas that are interconnected to form hierarchical processing streams. Our preliminary data indicates that a higher auditory cortical area, A2, selectively represents multi-frequency sounds with coincident onset timings. We hypothesize that inhibitory circuits in A2 gate the integration of tones in a synchrony-dependent manner, and this gating gives mice an ability to detect harmonic sounds. Our goal is to examine this hypothesis by taking advantage of cutting-edge two-photon calcium imaging and in vivo whole-cell recording techniques that are available in mice. To achieve our goal, this project aims to (1) Determine the distinct spectro-temporal integration across auditory areas (macroscopic and cellular-level calcium imaging), (2) Dissect the circuit mechanisms underlying spectro-temporal integration (in vivo whole-cell recordings), and (3) Determine the perceptual roles of higher auditory cortices in processing harmonics (optogenetics during behaviors). Findings in the simple mouse cortex should provide a first step towards the ultimate understanding of the “feature binding” circuits that enable verbal communication, and how they fail in diseased brains.