Cortical circuits for the integration of parallel short-latency auditory pathways

用于整合并行短延迟听觉通路的皮层电路

• 批准号: 10524362
• 负责人: Hiroyuki Kato
• 金额: $ 153.83万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10524362
• 关键词: Acoustics; Affect; Anatomy; Auditory; Auditory area; Auditory system; Automobile Driving; Behavior; Behavioral; Brain; Cell Nucleus; Cerebral cortex; Cochlear nucleus; Data; Development; Electrophysiology (science); Foundations; Functional disorder; Future; Gene Expression; Geniculate body structure; Goals; Head; Hearing problem; In Vitro; Inferior Colliculus; Knowledge; Label; Link; Maps; Medial; Mediating; Modality; Mus; Neurons; Neurosciences; Pathway interactions; Perception; Peripheral; Presynaptic Terminals; Research; Role; Running; Sensory; Shapes; Slice; Stimulus; Structure; Synapses; Testing; Thalamic structure; Time; Transgenic Mice; Whole-Cell Recordings; Work; anatomical tracing; auditory pathway; auditory processing; auditory thalamus; awake; cell type; experience; experimental study; in vivo; inhibitory neuron; insight; multisensory; neural circuit; novel; operation; optogenetics; patch clamp; preservation; response; sensory integration; sound

PROJECT SUMMARY How our brain achieves coherent perception by integrating information from parallel sensory pathways distributed across space and time remains a central question in neuroscience. In the auditory system, sound information reaches the cortex via the lemniscal (“primary”) and non-lemniscal (“secondary”) pathways. The non-lemniscal pathways have often been described as slower integrators of multi-sensory information, in contrast to the roles of the lemniscal pathways as fast and reliable relays for sound inputs. However, the contribution of the non-lemniscal pathways in driving fast cortical responses and how they interact with the lemniscal pathways during sound processing are still matters of debate. Our preliminary electrophysiology experiments show that layer 6 (L6) of not only the primary but also the secondary auditory cortex receives sound inputs whose latency can be shorter than the L4 lemniscal inputs. Surprisingly, our retrograde tracing demonstrates that this short-latency L6 input originates from the non-tonotopic parts of the auditory thalamus, supporting the role of the non-lemniscal pathway in fast sensory processing. Building on this exciting finding, we will combine anatomical tracing, in vitro/in vivo electrophysiology, optogenetics, and behavior to delineate this non-classical pathway and determine how it interacts with the lemniscal pathway to regulate cortical sensory processing. Specifically, we will examine the hypothesis that short-latency non-lemniscal inputs onto L6 regulate cortical sound processing in a timing-dependent manner and control the tuning and temporal fidelity of sound responses. To achieve this goal, this project aims to (1) Delineate the anatomy of the fast non- lemniscal pathway from the cochlear nucleus to the auditory cortex using both anatomical tracing and in vivo unit recordings, (2) Determine the synaptic impact of the non-lemniscal input onto cortical cell types by performing targeted whole-cell recordings in cortical slices while simultaneously activating L6-targeting thalamic inputs, and (3) Identify the roles of the fast non-lemniscal input in cortical sound processing in vivo by optogenetically manipulating thalamic inputs onto L6 during unit recordings in the mice performing sound- guided behaviors. Through our research, we seek to provide a more holistic understanding of auditory processing across the two major ascending pathways. Since parallel thalamocortical inputs onto L4 and L6 are conserved across sensory modalities, results from this project will provide insights into the generalizable principles underlying the cortical circuitry of sensory integration. Ultimately, these studies will help the future development of targeted treatments for not only hearing disorders but also other sensory integration dysfunctions.

项目摘要 我们的大脑如何通过整合来自平行感觉通路的信息来实现连贯感知 在空间和时间上的分布仍然是神经科学的中心问题。在听觉系统中，声音 信息通过丘系（“初级”）和非丘系（“次级”）通路到达皮层。的 非丘系通路通常被描述为多感觉信息的较慢的整合者， 与丘系通路作为声音输入的快速和可靠中继的作用形成对比。但 非丘系通路在驱动快速皮层反应中的作用以及它们如何与 在声音处理过程中的丘系通路仍然是有争议的问题。我们初步的电生理检查 实验表明，第6层（L 6）不仅接收初级听觉皮层，而且接收次级听觉皮层 声音输入，其延迟可以短于L4丘系输入。令人惊讶的是，我们的逆行追踪 表明这种短潜伏期L 6输入来源于听觉丘脑的非音调性部分， 支持非丘系通路在快速感觉处理中的作用。基于这一令人兴奋的发现， 我们将结合联合收割机解剖追踪、体外/体内电生理学、光遗传学和行为学来描绘 这一非经典途径，并确定它如何与丘系通路相互作用，以调节皮质 感觉处理具体来说，我们将研究的假设，短潜伏期非丘系输入到 L 6以时间依赖的方式调节皮层声音处理，并控制调谐和时间 声音响应的保真度。为了实现这一目标，本项目旨在（1）描绘快速非- 耳蜗核至听皮层丘系通路的解剖学追踪和活体研究 单位记录，（2）确定非丘系输入对皮质细胞类型的突触影响， 在皮层切片中进行靶向全细胞记录，同时激活L 6靶向 丘脑的输入，（3）确定快速非丘系输入在皮质声音处理中的作用， 光遗传学操纵丘脑输入到L 6在单位记录在小鼠执行声音- 引导行为。通过我们的研究，我们试图提供一个更全面的了解听觉 在两条主要的上升路径上进行处理。由于L4和L 6上的丘脑皮层平行输入是 保存跨感官形式，从这个项目的结果将提供深入了解的普遍性 感觉整合皮层回路的基本原理。最终，这些研究将有助于未来 开发针对听力障碍和其他感觉统合的靶向治疗方法 功能障碍