Cholinergic Modulation of Cochlear Plasticity

耳蜗可塑性的胆碱能调节

• 批准号: 10677802
• 负责人: Amanda M. Lauer
• 金额: $ 49.96万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10677802
• 关键词: Acoustic Trauma; Acoustics; Aging; Animals; Auditory; Brain; Calcium Signaling; Cell physiology; Cochlea; Development; Electron Microscopy; Feedback; Hair Cells; Hearing; Knockout Mice; Morphology; Mus; Play; Research Proposals; Role; Structure; Synapses; System; aged; cell age; cholinergic; cholinergic synapse; critical developmental period; gain of function; hearing impairment; mechanotransduction; nerve supply; post-trauma; synaptic function; synaptic inhibition

This research proposal examines the impact of acoustic trauma, development and aging on the innervation of cochlear hair cells, with particular focus on the role of the efferent system. Emerging evidence suggests that afferent and efferent synapses interact in undefined ways during a developmental critical period, and in parallel with altered acoustic function. How might such interactions occur? Does activity of the hair cell determine synaptic arrangements, or do synapses ‘compete’ for territory? In particular, do efferent inputs play an instructive role in the differentiation of hair cell function? Or, are efferent (and afferent) synapses dependent upon changes in hair cell excitation? To approach these questions, hair cell excitability and synaptic function will be detailed before and after acoustic trauma in AChR-null (α9 null) mice, and in those with gain of function AChRs (α9L9’T). Auditory function and synaptopathy will be assessed in aging animals in α9 null and α9L9’T mice. Finally, the developmental maturation of synapses on IHCs will be examined in TMC2 mechanotransduction null mice.

这项研究建议检查声学创伤，发展和衰老对 耳蜗毛细胞的神经，特别关注有效系统的作用。 新兴证据表明，传入和有效的突触以不确定的方式相互作用 在发育的关键时期，并与声函数改变。怎么可能 发生这种互动？毛细胞的活性确定突触排列，还是做 突触“竞争”领土？特别是，有效的输入在 毛细胞功能的区分？或者，取决于有效（和传入）的突触 毛细胞兴奋的变化？要解决这些问题，毛细细胞兴奋和突触 功能将在ACHR-NULL（α9NULL）小鼠中的声学创伤之前和之后详细介绍，并在 具有功能ACHR的增益（α9L9'T）的人。听觉功能和突触病将是 在α9NULL和α9L9的衰老动物中评估。最后，发展成熟 IHC上的突触将在TMC2机械转导无小鼠中检查。

项目成果

Cochlear hair cells: The sound-sensing machines.

• DOI: 10.1016/j.febslet.2015.08.030
• 发表时间: 2015-11-14
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: Goutman JD;Elgoyhen AB;Gómez-Casati ME
• 通讯作者: Gómez-Casati ME

Chromosome location and characterization of the human nicotinic acetylcholine receptor subunit alpha (alpha) 9 (CHRNA9) gene.

人类烟碱乙酰胆碱受体亚基 α (α) 9 (CHRNA9) 基因的染色体定位和特征。

• DOI: 10.1159/000069804
• 发表时间: 2002
• 期刊: Cytogenetic and genome research
• 影响因子: 1.7
• 作者: Lustig,LR;Peng,H
• 通讯作者: Peng,H

Nicotine evoked efferent transmitter release onto immature cochlear inner hair cells.

尼古丁引起传出递质释放到未成熟的耳蜗内毛细胞上。

• DOI: 10.1152/jn.00097.2020
• 发表时间: 2020
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Zhang,Y;Glowatzki,E;Roux,I;Fuchs,PA
• 通讯作者: Fuchs,PA

The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?

• DOI: 10.1080/14728222.2022.2047931
• 发表时间: 2022-03
• 期刊: EXPERT OPINION ON THERAPEUTIC TARGETS
• 影响因子: 5.8
• 作者: Belen Elgoyhen, Ana

Differential Contribution of Subunit Interfaces to α9α10 Nicotinic Acetylcholine Receptor Function.

• DOI: 10.1124/mol.116.107482
• 发表时间: 2017-03
• 期刊: Molecular pharmacology
• 影响因子: 3.6
• 作者: Boffi JC;Marcovich I;Gill-Thind JK;Corradi J;Collins T;Lipovsek MM;Moglie M;Plazas PV;Craig PO;Millar NS;Bouzat C;Elgoyhen AB
• 通讯作者: Elgoyhen AB