Development of hemispheric specializations during Auditory Cortex critical periods

项目摘要 尽管新皮层的组织包括许多一致的连接模式 在细胞之间，单个皮层区域也包含独特的电路图案，使它们能够 执行特定功能。其中一个特化是左半球语言优势， 这在人类中是众所周知的。老鼠和其他哺乳动物也使用发声来进行社交和 生殖的相互作用，并显示半球的不对称性，在处理这些发声。 这种相似性表明，可能存在共同的声音处理机制， 使用动物模型中可用的强大电路分析工具进行研究。该提案重点 在老鼠的听觉皮层上，它优先对特定的声音组合做出反应。 在频率和时间上，以上下文相关的方式， 物种特异性发声的组成部分。我们的工作揭示了连通性差异 左右听觉皮层之间的差异，这是听觉体验依赖的，但它是 不知道这些差异是如何产生的。这个实验室的长期目标是 听觉皮层中的一种特殊回路特征，是编码信息的能力的基础 这对社会交流很重要， 沟通障碍本提案的总体目标是确定半球 关键时期的时间差异，以及行为相关性的出现 侧化加工这项提议将检验半球的工作假设， 听觉处理的专门化是由不同年龄段的人之间成熟率的差异引起的。 左右听觉皮层将通过大脑半球来识别成熟差异。 与关键期的开始和结束相关的分子标志物的比较，以及电路- 使用电生理学的基序开发。我们还将确定出现的差异， 侧化功能与行为分析。本提案中的初步数据表明， 左右听觉皮层的成熟率有显著差异。这 这种方法是创新的，因为它是第一个研究解剖半球的差异， 电路和功能水平的听觉皮层，并测试其起源的一个新的假设。的 这里提出的研究是重要的，因为它有望揭示基本的见解， 听觉皮层功能的专业化发展，这将提供强大的工具， 来研究听觉皮层是如何对交流声音进行编码的， 神经发育障碍的症状

Project Summary Although the organization of the neocortex includes many consistent patterns of connections between cells, individual cortical areas also contain unique circuit-motifs that enable them to perform specific functions. One such specialization is left-hemisphere language dominance, which is well known in humans. Mice and other mammals also use vocalizations for social and reproductive interactions and show hemispheric asymmetry in processing these vocalizations. This similarity suggests there may be shared mechanisms for vocal processing that can be studied using the powerful circuit analysis tools available in animal models. This proposal focuses on the mouse auditory cortex, which preferentially responds to particular sound combinations across frequencies and time, in a context-dependent fashion, and thus encodes important components of species-specific vocalizations. Our work has revealed connectivity differences between the left and right auditory cortices that are hearing-experience dependent, but it is unknown how these differences arise. The long-term goal of this laboratory is to identify specialized circuit features in the auditory cortex that underlie the ability to encode information that is important for social communication and how they go awry in neurodevelopmental communication disorders. The overall objective of this proposal is to identify hemispheric differences in the timing of critical periods, and emergence of the behavioral relevance of lateralized processing. This proposal will test the working hypothesis that hemispheric specializations in auditory processing arise from differences in the maturation rate between the left and right auditory cortices. Maturational differences will be identified through hemispheric comparison of molecular markers related to the onset and closure of critical periods, and circuit- motif development using electrophysiology. We will also identify differences in the emergence of lateralized function with behavioral assays. Preliminary data in this proposal demonstrate significant differences in the maturation rate between the left and right auditory cortices. This approach is innovative because it is the first study to dissect hemispheric differences at the circuitry and functional level in the auditory cortex, and test a novel hypothesis of its origin. The research proposed here is significant because it is expected to reveal fundamental insights into the development of specializations in auditory cortical function, which will provide powerful tools to study how the auditory cortex encodes communication sounds and how this encoding goes awry in neurodevelopmental disorders.