Cortical circuits for temporal integration of multi-frequency sounds

项目摘要 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捆绑在一起 它们属于同一个声源，可以识别单个声音对象。在人类中， 将声音成分转换为单一声音感知依赖于它们开始的精确同步（< 30 ms窗口） 时间，这种分组在我们对语言的感知中起着关键作用。尽管这很重要 “感觉特征结合”，我们仍然知道很少关于神经回路机制的基础上，我们如何 大脑整合频谱和时间分布的声音输入。为了弥补这一知识差距， 该项目将使用小鼠听觉皮层来定义谐波声音结合的神经元回路， 一个模型系统老鼠的听觉皮层由五个区域组成，它们相互联系，形成层次结构。 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， 表示具有重合起始时间的多频率声音。我们假设A2区的抑制回路 以同步依赖的方式门控音调的整合，这种门控使小鼠能够检测到 和声我们的目标是利用尖端的双光子来检验这一假设 钙成像和体内全细胞记录技术，可在小鼠中使用。为了实现我们的目标， 本项目旨在（1）确定听觉区域（宏观）上不同的频谱-时间整合 和细胞水平的钙成像），（2）解剖频谱-时间整合的电路机制 (in活体全细胞记录），（3）确定高级听觉皮层在处理中的感知作用 谐波（行为过程中的光遗传学）。在简单的小鼠大脑皮层中的发现应该提供了第一步 走向最终理解的“功能绑定”电路，使语言交流，以及如何 它们在病变的大脑中失效。

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.