Development of hemispheric specializations during Auditory Cortex critical periods

项目摘要 尽管新大脑皮层的组织包括许多一致的连接模式 在细胞之间，单独的皮质区域也包含独特的回路图案，使它们能够 执行特定的职能。其中一个特长是左半球的语言优势， 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 在处理这些发声时，生殖相互作用和表现出半球的不对称性。 这种相似性表明，可能存在共享的语音处理机制，可以 使用动物模型中可用的强大电路分析工具进行了研究。这项提案将重点放在 在小鼠的听觉皮质上，它优先对特定的声音组合做出反应 以上下文相关的方式跨频率和跨时间，从而编码重要的 物种特定发声的组成部分。我们的工作揭示了连接的差异 左右两个听觉皮层之间依赖于听觉经验，但它 不知道这些差异是如何产生的。这个实验室的长期目标是确定 听觉皮质中的特殊回路特征，是编码信息能力的基础 这对于社会交流以及它们在神经发育中是如何出错的很重要 沟通障碍。这项提议的总体目标是识别半球 关键时期的时间差异，以及出现的行为相关性 偏侧化处理。这一提议将检验工作假说，即半球 听觉处理的专门化是由于两种语言的成熟率不同 左右两个听觉皮质。成熟的差异将通过半球来识别 与临界期开始和结束相关的分子标记的比较，以及回路- 利用电生理学进行基序发育。我们还将确定在出现 用行为分析对功能进行定侧化。这份提案中的初步数据表明 左、右听皮层成熟率有显著差异。这 方法是创新的，因为它是第一个在 在听觉皮质的电路和功能水平，并测试其起源的新假说。这个 这里提出的研究意义重大，因为它有望揭示 听觉皮质功能专业化的发展，这将提供强大的工具 为了研究听觉皮质如何对交流声音进行编码以及这种编码是如何进行的 神经发育障碍中的歪斜。

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.