Cell-type basis for auditory processing in the inferior colliculus

下丘听觉处理的细胞类型基础

• 批准号: 10608768
• 负责人: Li I Zhang
• 金额: $ 58.86万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-09 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10608768
• 关键词: Address; Anatomy; Animals; Auditory; Auditory Perception; Auditory area; Auditory system; Behavior; Bioinformatics; Brain; Brain Stem; Cataloging; Cell Nucleus; Communication; Coupled; Development; Dorsal; Electrophysiology (science); Endowment; Exhibits; Feedback; Genes; Genomics; Hearing; Ice; Impairment; Inferior Colliculus; Label; Mediating; Methods; Molecular; Mus; Neural Pathways; Neurons; Nitric Oxide Synthase; Nitric Oxide Synthase Type I; Output; Pattern; Physiological; Population; Procedures; Property; Research; Role; Slice; Somatostatin; Source; Spatial Distribution; Specific qualifier value; Synapses; Testing; Transgenic Organisms; Viral; Whole-Cell Recordings; Work; auditory processing; awake; base; biomarker identification; candidate marker; cell type; excitatory neuron; hearing impairment; in vivo; inhibitory neuron; insight; molecular marker; optogenetics; response; screening; single nucleus RNA-sequencing; sound; transcriptome sequencing

Project Summary As a major hub of the central auditory system for hearing, the inferior colliculus (IC) receives both bottom-up input from auditory brainstem nuclei, as well as feed-back input from the auditory cortex (AC). IC contributes importantly to the processing of essential features of sounds for communication and localization. Impaired IC processing has been associated with various hearing deficits. However, despite extensive studies of central auditory processing in IC, our understanding of cell-type-specific circuit mechanisms underlying the functional roles of the IC remains limited. In particular, how different types of neurons in the three anatomical and functional subdivisions of IC, the central nucleus (ICc), dorsal cortex (ICd), and external cortex (ICe), interact with each other and contribute differentially to the auditory processing of IC remains largely unclear. Addressing this question requires identification of molecular markers for cell types specifically located in each of the subdivisions. With 10X Genomics single-nucleus RNA sequencing (snRNAseq), we made initial efforts in screening molecular markers for different neuronal populations of IC. By identifying and verifying specific markers for IC subdivisions and exploiting corresponding transgenic Cre mouse lines for the selected marker genes, we will then characterize the anatomical connections and auditory response properties of the selected cell type and its functional role in auditory processing functions. Our preliminary snRNAseq results suggest two potential molecular markers specifically labeling subpopulations of excitatory neurons in the IC cortex. Their verification will endow us with unique opportunities to investigate the specific and diverse functional roles of ICd in auditory perception and behavior. Cutting-edge approaches in electrophysiology, anatomy, and optogenetics coupled with intersectional or projection-based tagging will be applied to address the differential functional contribution of diverse neuronal types in ICd as well as the distinct underlying circuitry mechanisms.

项目摘要 作为听觉中枢系统的主要中枢，下丘（IC）接受 来自听觉脑干核团的自下而上的输入，以及来自听觉皮层（AC）的反馈输入。 IC对处理声音的基本特征以进行交流做出了重要贡献， 本地化受损的IC处理与各种听力缺陷有关。然而，在这方面， 尽管对IC的中央听觉处理进行了广泛的研究，但我们对细胞类型特异性的理解 作为IC功能作用基础的电路机制仍然有限。尤其是， 在IC的三个解剖和功能细分中的神经元类型，中央核（ICc）， 背侧皮层（ICd）和外皮层（ICe）相互作用，并对大脑皮层的功能产生不同的影响。 IC的听觉处理仍然很不清楚。解决这个问题需要确定 细胞类型的分子标记，特别是位于每一个细分。关于10X Genomics 单核RNA测序（snRNAseq），我们在筛选分子标记方面做了初步的努力 对于IC的不同神经元群体。通过识别和验证IC细分的特定标记 并利用相应的转基因Cre小鼠品系的所选标记基因，然后我们将 表征所选细胞类型的解剖学连接和听觉响应特性， 它在听觉处理功能中的作用。我们的初步snRNAseq结果表明， 特异性标记IC皮质兴奋性神经元亚群的潜在分子标记物。 它们的核查将使我们有独特的机会调查具体和多样的 ICd在听觉感知和行为中的功能作用。尖端方法， 电生理学、解剖学和光遗传学与交叉或基于投影的标记相结合 将被应用于解决不同类型的神经元在ICd中的不同功能贡献，以及 作为不同的底层电路机制。