Identification of Cellular Phenotypes in the Auditory Forebrain

听觉前脑细胞表型的鉴定

基本信息

批准号：
9226042
负责人：
TROY A. HACKETT
金额：
$ 33.58万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9226042
关键词：
Acetylcholine Address Adenosine Adolescent Adult Age Aging Anatomy Area Astrocytes Auditory Auditory area Auditory system Autistic Disorder Award Base of the Brain Biological Biological Assay Brain Brain region Categories Cell Nucleus Cells Cerebral cortex Clinical Code Communication impairment Communities Data Databases Development Dimensions Dopamine Family Fluorescent in Situ Hybridization Foundations Gene Expression Gene Family Gene Proteins Gene Targeting Genes Glutamates Glycine Goals Hearing Image Immunohistochemistry Impairment Individual K-18 conjugate Laboratories Libraries Location Manuscripts Medial geniculate body Mentors Messenger RNA Microglia Mining Modeling Molecular Molecular Profiling Mus Neuroglia Neurons Neurotransmitter Receptor Norepinephrine Oligodendroglia Ontology Pathology Pathway interactions Pattern Pharmacology Study Phenotype Population Positioning Attribute Process Prosencephalon Publishing RNA Receptor Cell Receptor Gene Research Resources Role Serotonin Signal Transduction Site Specificity Stroke Structure Thalamic structure Therapeutic Therapeutic Intervention Time Tinnitus Tissues Transgenic Organisms Untranslated RNA Work auditory pathway base cell type gamma-Aminobutyric Acid hearing impairment improved molecular sequence database neurobiological mechanism neurophysiology neurotransmission next generation sequencing optogenetics postnatal programs public health relevance receptor systems research therapeutic effectiveness tool transcriptome transmission process user-friendly web site

项目摘要

DESCRIPTION (provided by applicant): In central auditory systems research, the basic layout and wiring diagrams of major brain areas in the most widely used model species have been generated. Neuroanatomical efforts are now primarily focused on the characterization of specific circuits. An important and rudimentary component in that process is to (1) identify the functionally-distinct cellular phenotypes that comprise each brain region; and (2) determine their precise locations in the pathway. The tools to acquire these data are now available. In this proposal, we have used the transcriptome (mRNA sequencing database) of the auditory forebrain to identify 72 (of 140) neurotransmitter receptor genes that are significantly expressed in the primary auditory cortex and medial geniculate body. Using multiplexed fluorescence in situ hybridization assays, each of those genes will be localized to each of 5 major cell types (neurons: glutamatergic, GABAergic)(glia: astrocytes, oligodendrocytes, microglia). Analyses of the co-expression patterns will permit us to identify and localize distinct neuronal and glial phenotypes in the each brain region based on their gene expression profiles. These data will expand understanding of the mechanisms that govern neurotransmission and plasticity at the cellular level, and permit greater specificity in the targeting of functionally-distinct cell typesfor neurophysiological study. More generally, the sequencing- guided approach adds a new dimension to studies of brain structure and function, and provides an expanded foundation for ongoing efforts to characterize the neurobiological mechanisms associated with communication disorders of all types. A comprehensive understanding of the molecular mechanisms that govern function in the auditory system is essential for conceiving of and improving existing therapeutic approaches that address impaired auditory function in clinical populations (hearing loss, autism, aging and stroke).

描述（由申请人提供）：在中枢听觉系统研究中，已经生成了最广泛使用的模型物种的主要大脑区域的基本布局和接线图，神经解剖学工作现在主要集中在特定电路的表征上。该过程的基本组成部分是（1）识别构成每个大脑区域的功能不同的细胞表型；以及（2）确定它们在通路中的精确位置。根据提议，我们使用听觉前脑的转录组（mRNA 测序数据库）来鉴定 72 个（共 140 个）神经递质受体基因，这些基因在初级听觉皮层和内侧膝状体中显着表达，每个基因均采用多重荧光原位杂交测定。这些基因将定位于 5 种主要细胞类型（神经元：谷氨酸能、GABA 能）（神经胶质细胞：星形胶质细胞、少突胶质细胞、小胶质细胞）中的每一种。对共表达模式的分析将使我们能够根据基因表达谱来识别和定位每个大脑区域中不同的神经和神经胶质表型，这些数据将扩大对细胞水平上控制神经传递和可塑性的机制的理解。更广泛地说，测序引导的方法为大脑结构和功能的研究增加了一个新的维度，并为表征神经生物学机制的持续努力提供了扩展的基础。全面了解控制听觉系统功能的分子机制对于构思和改进解决临床人群听觉功能受损（听力损失、自闭症、衰老和中风）的现有治疗方法至关重要。。