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.

项目总结