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.

项目概要 我们的大脑如何通过整合来自并行感觉通路的信息来实现连贯的感知 在听觉系统中，声音在空间和时间上的分布仍然是神经科学的一个核心问题。 信息通过丘系（“初级”）和非丘系（“次级”）途径到达皮层。 非丘脑通路通常被描述为多感觉信息的较慢整合者， 与丘系通路作为声音输入的快速可靠中继器的作用形成鲜明对比。 非丘脑通路在驱动快速皮质反应中的贡献以及它们如何与 声音处理过程中的丘系通路仍然是我们初步电生理学争论的问题。 实验表明，初级听觉皮层和次级听觉皮层的第 6 层 (L6) 都接收 令人惊讶的是，我们的逆行追踪的延迟可能比 L4 丘系输入更短。 证明这种短延迟 L6 输入源自听觉丘脑的非音调部分， 基于这一令人兴奋的发现，支持非丘脑通路在快速感觉处理中的作用。 我们将结合解剖追踪、体外/体内电生理学、光遗传学和行为来描绘 这种非经典途径，并确定它如何与丘系途径相互作用来调节皮质 具体来说，我们将检查短延迟非神经系输入的假设。 L6 以依赖于时间的方式调节皮质声音处理并控制音调和时间 为了实现这一目标，该项目旨在 (1) 描绘快速非响应的解剖结构。 使用解剖追踪和体内从耳蜗核到听觉皮层的丘系通路 单位记录，（2）确定非丘系输入对皮质细胞类型的突触影响 在皮质切片中进行靶向全细胞记录，同时激活 L6 靶向 丘脑输入，以及（3）通过以下方式确定快速非丘脑输入在体内皮质声音处理中的作用 在执行声音的小鼠的单元录音过程中，通过光遗传学操作 L6 上的丘脑输入 通过我们的研究，我们试图提供对听觉的更全面的理解。 由于 L4 和 L6 上的丘脑皮质输入是平行的，因此可以通过两个主要的上升通路进行处理。 该项目的结果在各种感官模式中都保守，将提供对可推广的见解 最终，这些研究将有助于未来感觉统合的皮层电路的基本原理。 开发不仅针对听力障碍而且针对其他感觉统合的靶向治疗 功能障碍。