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.

这项研究计划探讨了声学创伤，发展和老化对 耳蜗毛细胞的神经支配，特别关注传出系统的作用。 新出现的证据表明传入和传出突触以不确定的方式相互作用 在发育的关键时期，并与改变的声学功能并行。什么样子 这种互动会发生吗？毛细胞的活动决定突触的排列，还是 突触“竞争"领土？特别是，传出输入是否在 毛细胞功能分化或者，传出（和传入）突触依赖于 毛细胞兴奋度的变化为了解决这些问题，毛细胞兴奋性和突触 将详细描述AChR-null（α9 null）小鼠声损伤前后的功能， AChRs（α 9 L9 'T）功能增强者。听觉功能和突触病 在α9 null和α 9 L9 'T小鼠中的衰老动物中进行评估。最后， 将在TMC 2机械转导无效小鼠中检查IHC上的突触。

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

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

Onset of cholinergic efferent synaptic function in sensory hair cells of the rat cochlea.

• DOI: 10.1523/jneurosci.2743-11.2011
• 发表时间: 2011-10-19
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Roux I;Wersinger E;McIntosh JM;Fuchs PA;Glowatzki E
• 通讯作者: Glowatzki E