Functional organization of the auditory corticocollicular system

听觉皮质皮质系统的功能组织

• 批准号: 8888751
• 负责人: DANIEL A LLANO
• 金额: $ 37.86万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8888751
• 关键词: Acoustic Stimulation; Aphasia; Area; Auditory; Auditory area; Auditory system; Autistic Disorder; Brain; Cell Nucleus; Cells; Characteristics; Clinical; Communication; Communication impairment; Cues; Data; Deposition; Disease; Dyslexia; Electric Stimulation; Environment; Flavoproteins; Fluoro-Gold; Foundations; Glutamates; Goals; Hearing; Hearing problem; Human; Image; Individual; Inferior Colliculus; Injection of therapeutic agent; Knowledge; Label; Language; Lasers; Light; Maps; Microinjections; Mus; Neurons; Optics; Output; Pathway interactions; Patients; Pattern; Physiological; Physiology; Play; Preparation; Process; Property; Role; Sensory Process; Shapes; Signal Transduction; Slice; Stream; Structure; Synapses; System; Techniques; Testing; Tracer; Whole-Cell Recordings; Work; brain pathway; cell type; in vivo; mouse model; neuromechanism; novel; optical imaging; photolysis; public health relevance; reconstruction; relating to nervous system; sound; therapeutic development

 DESCRIPTION (provided by applicant): The ability to extract meaning from sounds, even when degraded, is critical for normal hearing. A key strategy employed by the auditory system during acoustically-challenging situations is the use of contextual cues to disambiguate cluttered signals. Importantly, many patients with language-related disorders, such as aphasia, autism and dyslexia, have difficulties harnessing such contextual cues. The neural mechanisms by which high-level information can be used to shape lower-level sensory processing are not yet known. A potential substrate for this type of processing is the massive top-down projection system emanating from virtually every level of the auditory system. In this project, we will provide a functional characterization of one of the largest of these projections: the auditory corticocollicular system. The corticocollicular system can rapidly and profoundly change the tuning of neurons in the inferior colliculus, but key aspects about its organization are not known. We hypothesize that this system comprises at least two functionally distinct sub- systems; one from cortical layer 5 and another from cortical layer 6. Using the mouse model, the cortical distribution of layer 5 and 6 neurons that project to small regions of the inferior colliculus willbe reconstructed and compared. Our early data suggest that input from layer 6 emanates from a more widespread area than layer 5 and tends to predominate in the non-primary parts of the auditory cortex. In addition, we will combine in vivo transcranial flavoprotein autofluoresence imaging with quantitative neuronal reconstructions to compare the projection patterns of layer 5 vs. layer 6 cortical projections to the inferior colliculus. Finally, using a novel corticocolliculr brain slice preparation and laser photostimulation, we will compare the synaptic properties of layer 5 and 6 corticocollicular synapses. Successful completion of this project will provide the first circuit-level characterization of this important pathway and will lay the groundwork for a greater understanding of how top-down modulatory systems break down during disorders of communication.

 描述(申请人提供)：从声音中提取意义的能力，即使是在退化的情况下，对正常的听力来说也是至关重要的。听觉系统在具有声学挑战性的情况下采用的一个关键策略是使用上下文线索来消除杂乱信号的歧义。重要的是，许多患有语言相关障碍的患者，如失语症、自闭症和阅读障碍，都难以利用这些上下文线索。高级信息可以用来塑造低级感觉处理的神经机制尚不清楚。这类处理的一个潜在底物是巨大的自上而下的投影系统，该系统几乎来自听觉系统的每一级。在这个项目中，我们将提供这些投射中最大的一个：听觉皮质-小脑系统的功能特征。皮质小脑系统可以迅速而深刻地改变下丘神经元的调谐，但关于其组织的关键方面尚不清楚。 我们假设该系统至少包括两个功能不同的子系统：一个来自皮质第5层，另一个来自皮质第6层。利用小鼠模型，将重建并比较投射到下丘小区域的第5层和第6层神经元的皮质分布。我们的早期数据表明，来自第六层的输入来自比第五层更广泛的区域，并倾向于在听觉皮质的非初级部分占据主导地位。此外，我们将结合活体经颅黄素蛋白自身荧光成像和定量神经元重建来比较第5层和第6层皮质投射到下丘的投影模式。最后，使用一种新的皮质小脑切片制备和激光光刺激，我们将比较5层和6层皮质小脑突触的突触特性。该项目的成功完成将提供这一重要途径的第一个电路级别的表征，并将为更好地理解自上而下的调制系统如何在通信障碍期间崩溃奠定基础。