Modulation of sensory representations in the auditory cortex by callosal inputs

通过胼胝体输入调节听觉皮层的感觉表征

• 批准号: 10270400
• 负责人: Bernard Slater
• 金额: $ 3.41万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10270400
• 关键词: Acute; Address; Anatomy; Apical; Auditory; Auditory Hallucination; Auditory area; Auditory system; Axon; Brain; Brain Diseases; Calcium; Cells; Cerebral cortex; Code; Communication; Communication impairment; Contralateral; Corpus Callosum; Coupled; Cre driver; Dendrites; Development; Diagnosis; Diagnostic; Disease; Electrophysiology (science); Frequencies; Functional disorder; Glass; Head; Heterogeneity; Image; Injections; Interneurons; Knowledge; Language Disorders; Left; Light; Measures; Multiple Sclerosis; Mus; Neurons; Noise; Parvalbumins; Pathway interactions; Patients; Physiological; Play; Property; Pyramidal Cells; Role; Schizophrenia; Sensory; Signal Transduction; Silicon; Slice; Somatostatin; Sound Localization; Specificity; Synapses; Synaptophysin; Transgenic Mice; Vasoactive Intestinal Peptide; Viral; Work; age related; auditory processing; autism spectrum disorder; awake; calcium indicator; cell type; experimental study; imaging approach; implantation; in vivo; in vivo calcium imaging; insight; language processing; neuronal cell body; operation; optogenetics; photoactivation; response; sound; speech processing; tool; two-photon; voltage clamp

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.

项目摘要 左右听皮层之间的大脑半球间(颧骨)联系 建议参与语音定位和语音处理。此外， 听觉胼胝体投射的病理生理学被认为是语言的基础 与脑部疾病相关的缺陷和幻听。尽管有潜在的 皮质胼胝体投射在听觉加工中的重要性 大脑半球间连接的性质还没有被很好地理解。在这里，我们使用 清醒的头部固定小鼠的光遗传学、电生理和成像方法 确定初级听觉中的胼胝体投射对感觉编码的影响 皮质(A1)。最初在脑片上进行的解剖和生理实验将 确定膝盖骨输入的层次和细胞类型特异性。其次，急性和可逆性 线性硅探针对左侧听觉皮质的光遗传沉默研究 记录在清醒状态下右侧大脑皮质A1区，头部固定的小鼠将如何建立一个 大脑皮层影响另一侧的音调诱发反应。最后，我们将在体内使用两个- 用光子钙成像技术确定骨痂投射的紧张性组织 以及是否与目标区域的色调梯度相似。完成这项工作 这项工作将使我们深入了解大脑半球间胼胝体通路在大脑中的作用。 并将阐明它用来调节感觉的机制 申述。对这一途径的深入了解将有助于诊断和 治疗患有通讯障碍的患者，其中受累的膝盖骨 多发性硬化症、精神分裂症和自闭症等疾病。 假设：膝盖骨的输入调节了直视的听觉感觉表征， 层和单元格类型特定的方式。 目的1.确定骨痂投射的解剖学分布及其对 初级听觉皮层脑片的局部环路。 目的2.在清醒小鼠的初级听皮质中，确定胼胝体输入的作用。 目的3.明确轴突的频率响应特性和组织结构 利用双光子钙技术在清醒小鼠中发现起源于膝盖骨投射的双光子 成像。