Modulation of sensory representations in the auditory cortex by callosal inputs

项目摘要 左右听觉皮层之间的半球间（胼胝体）连接 建议参与声音定位和语音处理。此外，委员会认为， 提出了听觉胼胝体投射的病理生理学基础语言 与脑部疾病有关的缺陷和幻听。尽管潜在的 皮质胼胝体投射在听觉处理中的重要性， 半球间连接的性质还没有很好的理解。在这里，我们使用 光遗传学，电生理学和成像方法在清醒的，头部固定的小鼠， 确定胼胝体投射如何有助于初级听觉中的感觉编码 皮质（A1）。大脑切片的初步解剖学和生理学实验将 确定胼胝体输入的层和细胞类型特异性。其次，急性和可逆性 结合线性硅探针的左侧听觉皮层的光遗传学沉默 在清醒的头部固定的小鼠的右侧皮层的A1中的记录将建立一个 皮层影响另一个皮层的音调诱发反应。最后，我们将在体内使用两个- 光子钙成像确定胼胝体投射的色调结构 以及它是否与目标区域的色调梯度相似。完成本 这项工作将有助于深入了解大脑半球间胼胝体通路的功能， 听觉系统，并将阐明其用于调节感官的机制 表示。对这一途径的更深入了解将有助于诊断， 治疗胼胝体受影响的交流障碍患者， 多发性硬化症、精神分裂症和自闭症等疾病。 假设：胼胝体输入调节听觉感觉表征， 层和细胞类型特异性方式。 目标1.确定胼胝体投射的解剖分布及其对 初级听觉皮层的局部回路。 目标2.确定胼胝体输入在清醒小鼠初级听觉皮层中的作用。 目标3.定义轴突的频率响应特性和音调组织 清醒小鼠胼胝体投射的终扣 显像

ProjectAbstract Interhemispheric (callosal) connections between the right and left auditory cortex are suggested to participate in sound localization and speech processing. Furthermore, pathophysiology of auditory callosal projections is proposed to underlie language deficits and auditory hallucinations associated with brain disease. Despite the potential importance of cortical callosal projections in auditory processing, the functional properties of interhemispheric connections are not well understood. Here, we use optogenetic, electrophysiological and imaging approaches in awake, head-fixed mice to determine how callosal projections contribute to sensory coding in primary auditory cortex (A1). Initial anatomical and physiological experiments in brain slices will determine the layer and cell type specificity of callosal inputs. Next, acute and reversible optogenetic silencing of the left auditory cortex combined with linear silicon probe recordings in A1 of the right cortex in awake, head fixed mice will establish how one cortex influences tone-evoked responses in the other. Finally, we will use in vivo two- photon calcium imaging to determine the tonotopic organization of callosal projections and whether it is similar to the tonotopic gradient of target regions. Completion of this work will lend insight into the function of the interhemispheric callosal pathway in the auditory system and will shed light on the mechanisms it uses to modulate sensory representations. A deeper understanding of this pathway will inform the diagnosis and treatment of patients with communication disorders, where the callosum is impacted, in diseases such as multiple sclerosis, schizophrenia, and autism. Hypothesis: Callosal inputs modulate auditory sensory representations in a tonotopic, layer and cell type specific manner. Aim 1. Determine the anatomical distribution of callosal projections and their impact on local circuits in slices of primary auditory cortex. Aim 2. Determine the role of callosal input in primary auditory cortex in awake mice. Aim 3. Define the frequency response properties and tonotopic organization of axonal boutons originating from callosal projections in awake mice using two-photon calcium imaging.