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（由应用程序提供）：在中央听觉系统研究中，已经生成了最广泛使用的模型物种中主要大脑区域的基本布局和接线图。神经解剖学的努力现在主要集中在特定电路的表征上。该过程中的一个重要且基本的组成部分是（1）确定完成每个大脑区域的功能赋予的细胞表型；（2）确定其在路径中的精确位置。现在可用获取这些数据的工具。在此提案中，我们使用了听觉前脑的转录组（mRNA测序数据库）来识别72（140）神经递质受体基因，这些神经递质受体基因在主要的听觉皮层和中位数晶状体中显着表达。使用多重荧光原位杂交测定法，这些基因中的每一个都将定位于5种主要细胞类型（神经元：谷氨酸能，Gabaergic）（Glia：星形胶质细胞，少突胶质细胞，小胶质细胞）。对共表达模式的分析将使我们能够根据其基因表达谱在每个大脑区域中识别并定位不同的神经元和神经胶质表型。这些数据将扩大对在细胞水平上神经传递和可塑性的机制的理解，并在功能固定细胞类型的靶向神经生理学研究的靶向时具有更大的特异性。更一般而言，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，并为持续的努力提供了扩展的基础，以表征与各种类型沟通障碍相关的神经生物学机制。对控制听觉系统功能的分子机制的全面理解对于构思和改善现有的治疗方法至关重要，以解决临床人群中听觉功能受损（听力损失，自闭症，衰老和中风）。