Genetic dissection of auditory circuit assembly

听觉回路组件的基因解剖

基本信息

批准号：
10893217
负责人：
Lisa Goodrich
金额：
$ 9.32万
依托单位：
HARVARD MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10893217
关键词：
AMPA Receptors Acoustic Nerve Acoustic Trauma Affect Age Aging Anatomy Animal Model Animals Aromatase Auditory Auditory Perception Auditory Threshold Birth Brain Brain Stem Cochlea Code Complement DNA Data Development Dissection Ear Embryonic Development Endowment Exhibits Exposure to Fellowship GATA3 gene Gene Expression Gene Expression Regulation Genes Genetic Genetic Transcription Glutamate Receptor Glutamates Goals Hair Cells Hearing Heterogeneity Hispanic Graduate Student Human Laboratories Learning Life Maps Methods Molecular Morphology Mus Mutant Strains Mice Nature Nervous System Neurons Neurosciences Noise Pathway interactions Patients Persons Physiological Population Positioning Attribute Property Pythons Regulation Role SLC17A8 gene Side Signal Transduction Specific qualifier value Stimulus Synapses Talents Techniques Temporal bone structure Testing Time Training Training Support Underrepresented Students Viral aged calretinin conditional knockout experimental study falls graduate student hearing impairment hidden hearing loss improved meetings molecular subtypes nerve stem cell neuron development noise exposure normal hearing overexpression parent grant postnatal postsynaptic presynaptic progenitor programs repaired response ribbon synapse single-cell RNA sequencing sound spiral ganglion transcription factor transcriptome transmission process

项目摘要

Project Summary Spiral ganglion neurons (SGNs) encode everything an animal hears and send this information to the brain. In order to achieve rapid and reliable signal transmission, SGNs exhibit a number of specialized properties, including the ability to respond to glutamate via large, AMPA-receptor rich post-synaptic densities. Although all SGNs are glutamatergic, differences in the nature of their synapses and their responses to sound indicate that there are three distinct subtypes. High spontaneous firing rate (SR) SGNs have low thresholds and are likely the first to respond to sound. Low SR SGNs have higher thresholds and are proposed to improve the ability to detect sounds in noise; medium SR SGNs fall in between. These physiological differences are accompanied by parallel changes in the abundance of AMPA receptors and the size of the opposing pre-synaptic ribbon. Low SR SGN synapses are more vulnerable to the effects of noise exposure, which may be why some people have trouble understanding what they hear despite normal auditory thresholds. The long-term goal of this project is to understand how SGNs acquire the properties needed for the perception of sound. More immediately, we will define the intrinsic transcriptional networks that endow SGN subtypes with their distinct properties and functions. This supplement will support a talented Hispanic graduate student, Ms. Cynthia Moncada-Reid, for one year, so that she can receive additional training in mechanisms of gene regulation and collect preliminary data needed for a successful fellowship application. The goal of her dissertation is to dissect how two transcription factors, c- Maf and Mafb, interact with DNA to control different programs of gene expression in different SGN subtypes. To get started, she will perform a set of new experiments that build on findings from Aim 3 of the Parent Grant and that will prepare her to become an expert in the latest techniques used to study gene regulation in the laboratory. Her training will be further complemented by attendance at the ARO Midwinter Meeting, by completing courses on Python and R, and by attending an intensive course on molecular neuroscience. Collectively, these activities will expand her training and put her in an excellent position to make fundamental discoveries about the molecular basis of SGN subtype differentiation during development.

项目概要螺旋神经节神经元（SGN）对动物听到的所有信息进行编码，并将这些信息发送到大脑。在为了实现快速可靠的信号传输，SGN 表现出许多专门的特性，包括通过富含 AMPA 受体的突触后密度对谷氨酸做出反应的能力。虽然所有 SGN 具有谷氨酸能，其突触性质及其对声音的反应的差异表明：存在三种不同的亚型。高自发放电率 (SR) SGN 的阈值较低，很可能是首先对声音做出反应。低SR SGN具有更高的阈值，建议提高检测能力噪音中的声音；中型 SR SGN 介于两者之间。这些生理差异伴随着平行的 AMPA 受体的丰度和相对的突触前带的大小发生变化。低SR SGN 突触更容易受到噪音暴露的影响，这可能就是为什么有些人会遇到麻烦尽管听觉阈值正常，但仍能理解他们听到的内容。该项目的长期目标是了解 SGN 如何获得感知声音所需的属性。更立即，我们将定义了赋予 SGN 亚型独特属性和功能的内在转录网络。该补助金将为才华横溢的西班牙裔研究生 Cynthia Moncada-Reid 女士提供一年的支持，因此她可以接受基因调控机制方面的额外培训并收集所需的初步数据成功的奖学金申请。她论文的目标是剖析两个转录因子 c- Maf 和 Mafb 与 DNA 相互作用，控制不同 SGN 亚型中基因表达的不同程序。到开始后，她将根据家长补助金目标 3 的发现进行一系列新实验，这将使她成为实验室基因调控研究最新技术的专家。她的培训将通过参加 ARO 仲冬会议、完成课程得到进一步补充学习 Python 和 R，并参加分子神经科学强化课程。总的来说，这些活动将扩大她的培训并使她处于有利地位，以对分子进行基础发现发育过程中 SGN 亚型分化的基础。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.

DOI：
10.7554/elife.01341
发表时间：
2013-12-10
期刊：
eLife
影响因子：
7.7
作者：
Yu WM;Appler JM;Kim YH;Nishitani AM;Holt JR;Goodrich LV
通讯作者：
Goodrich LV

Connecting the ear to the brain: Molecular mechanisms of auditory circuit assembly.

DOI：
10.1016/j.pneurobio.2011.01.004
发表时间：
2011-04
期刊：
Progress in neurobiology
影响因子：
6.7
作者：
Appler JM;Goodrich LV
通讯作者：
Goodrich LV

Morphological and physiological development of auditory synapses.

DOI：
10.1016/j.heares.2014.01.007
发表时间：
2014-05
期刊：
HEARING RESEARCH
影响因子：
2.8
作者：
Yu, Wei-Ming;Goodrich, Lisa V.
通讯作者：
Goodrich, Lisa V.

Developmental profiling of spiral ganglion neurons reveals insights into auditory circuit assembly.

DOI：
10.1523/jneurosci.2358-11.2011
发表时间：
2011-07-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Lu CC;Appler JM;Houseman EA;Goodrich LV
通讯作者：
Goodrich LV

Gata3 is a critical regulator of cochlear wiring.

DOI：
10.1523/jneurosci.4703-12.2013
发表时间：
2013-02-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Appler JM;Lu CC;Druckenbrod NR;Yu WM;Koundakjian EJ;Goodrich LV
通讯作者：
Goodrich LV