Cortical circuits for temporal integration of multi-frequency sounds

项目总结 在日常生活中，即使面对多个声源，我们的大脑也会将频率成分捆绑在一起 属于同一来源并识别各个声音对象的。在人类中，光谱的分组 组件的单一声音感知依赖于其开始的精确同步性(&lt；30毫秒窗口 时间，而这种组合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”，我们仍然对我们的神经回路机制知之甚少。 大脑集成了频谱和时间分布的声音输入。为了解决这一知识差距，这一点 该项目将使用小鼠的听觉皮质来定义与谐音结合有关的神经元回路 一个模范系统。小鼠听皮层由五个区域组成，这些区域相互关联，形成层次结构 正在处理数据流。我们的初步数据表明，较高的听觉皮质区域A2选择性地 表示具有重合开始计时的多频率声音。我们假设A2中的抑制回路 以一种依赖于同步的方式对音调的整合进行选通，这种选通使老鼠能够检测到 和谐的声音。我们的目标是利用尖端的双光子来检验这一假说 可用于小鼠的钙成像和活体全细胞记录技术。为了实现我们的目标， 该项目的目标是(1)确定不同的跨听觉区域的谱-时间整合(宏观 和细胞水平的钙成像)，(2)剖析了频谱-时间整合的电路机制 (活体全细胞记录)，以及(3)确定高级听觉皮质在加工过程中的知觉作用 谐音(行为过程中的光遗传学)。在简单的小鼠皮质中的发现应该会提供第一步 最终理解实现语言交流的“功能绑定”电路，以及如何 它们在患病的大脑中失败了。

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.