Sensory Encoding in Hair Cells of the Zebrafish Lateral Line

斑马鱼侧线毛细胞的感觉编码

• 批准号: 9171195
• 负责人: Josef George Trapani
• 金额: $ 43.94万
• 依托单位: AMHERST COLLEGE
• 依托单位国家: 美国
• 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/9171195
• 关键词: Action Potentials; Afferent Neurons; Auditory; Auditory Perception; Auditory system; Brain; Bypass; Cochlear Implants; Communication impairment; Data; Dependence; Development; Devices; Dose; Electrophysiology (science); Frequencies; Future; Goals; Hair Cells; Hearing problem; Human; Ion Channel; Knowledge; Laboratories; Larva; Lead; Light; Location; Mammals; Mechanics; Medical Device; Modality; Music; Neurons; Optics; Outcome; Output; Pattern; Perception; Phase; Process; Proteins; Reflex action; Research; Research Personnel; Role; Sensory; Sensory Hair; Sensory Receptors; Speech; Stimulus; Study models; Synaptic Vesicles; System; Testing; Time; Training; Transgenic Organisms; Validation; Vertebrates; Voice; Work; Zebrafish; college; deafness; equilibration disorder; hearing impairment; in vivo; innovation; insight; lateral line; light gated; neurophysiology; optogenetics; programs; receptor; research study; response; ribbon synapse; sound; sound frequency; stimulus interval; transmission process; undergraduate student

The process by which the auditory system encodes low-frequency sounds such as those produced by the human voice and a grand piano is not entirely understood. Our long-term goal is to determine how hair cell sensory receptors encode stimulus features into representative sequences of electrical activity in sensory afferent neurons. Understanding this process relies on understanding how intrinsic hair-cell mechanisms contribute to encoded activity. The overall objective of this proposal is to examine sensory encoding in the lateral line system of larval zebrafish. Specifically, the central hypothesis of this proposal is that lateral-line hair cells encode stimulus intensity and duration within defined temporal patterns of afferent activity. The hypothesis was formulated through preliminary experiments on both wild type and transgenic larvae with hair-cell expression of the optogenetic protein, channelrhodhopsin-2 (ChR2), which allows for optical stimulation of hair cells instead of via activation of MET channels with mechanical stimuli. The central hypothesis will be tested with the following two specific aims: 1) Determine the relationship between stimulus features and activity parameters, which include the onset of activity, total amount of activity and the temporal patterns of the activity in wild type larvae; and 2) Compare neuron activity parameters between mechanical and optical stimulation of hair cells in transgenic larvae. Aim 1 will examine the dependence of activity parameters during manipulation of stimulus intensity, duration, and repetition. Experiments in Aim 2 will compare mechanically and optically evoked activity in two different transgenic zebrafish lines that combine optogenetics with wild type data to provide insight into the contribution of intrinsic hair-cell mechanisms on the parameters of afferent neuron activity. The rationale for this proposal is that examination of the relationship between input stimulus features and output activity parameters will further our understanding of auditory perception. The approach is innovative as it utilizes an in vivo approach with electrophysiology on single afferent neurons together with optogenetics to investigate low-frequency encoding in an intact larval zebrafish. Given the importance of low frequency auditory information, and that hair cells are remarkably conserved across vertebrates, our findings will be significant for understanding the function of the mammalian auditory system and will have a positive impact on the treatment of deafness and communication disorders, including the development of cochlear implants that can reliably encode low-frequency information.

听觉系统编码低频声音的过程，例如 人类的声音和宏伟的钢琴制作的人并不完全理解。我们的长期目标 是确定毛细胞感官受体如何编码刺激特征 感觉传入神经元中的电活动序列。了解这个过程依赖 了解固有的发型机制如何有助于编码活动。总体 该提案的目的是检查幼虫侧线系统中的感觉编码 斑马鱼。具体而言，该提议的中心假设是侧线毛细胞 在定义的传入活动时间模式中编码刺激强度和持续时间。这 通过对野生型和转基因的初步实验提出了假设 幼虫具有光遗传蛋白Channelrhodhopsin-2（ChR2）的发胶表达 允许对毛细胞进行光学刺激，而不是通过激活MET通道 机械刺激。中央假设将通过以下两个特定目的进行测试：1） 确定刺激特征和活动参数之间的关系，其中包括 活动的发作，活动总量和野生类型活动的时间模式 幼虫； 2）比较机械和光学刺激之间的神经元活性参数 转基因幼虫中的毛细胞。 AIM 1将检查活动参数的依赖性 在操纵刺激强度，持续时间和重复过程中。 AIM 2中的实验将 在两种不同的转基因斑马鱼线上进行机械和光学诱发的活性进行比较 将光遗传学与野生型数据结合在一起，以洞悉固有的贡献 传入神经元活性参数的发型机制。理由 建议是检查输入刺激特征与输出之间的关系 活动参数将进一步理解听觉感知。方法是 创新性，因为它利用了单个传入神经元电生理学的体内方法 与光遗传学一起研究完整的幼虫斑马鱼中的低频编码。 考虑到低频听觉信息的重要性，并且毛细胞非常明显 跨脊椎动物保守的，我们的发现对于理解的功能至关重要 哺乳动物的听觉系统，将对耳聋的治疗产生积极影响 和沟通障碍，包括可以可靠的人工耳蜗植入物的开发 编码低频信息。

项目成果

Mathematical Modeling and Analyses of Interspike-Intervals of Spontaneous Activity in Afferent Neurons of the Zebrafish Lateral Line.

• DOI: 10.1038/s41598-018-33064-z
• 发表时间: 2018-10-05
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Song S;Lee JA;Kiselev I;Iyengar V;Trapani JG;Tania N
• 通讯作者: Tania N

Teaching Dose-response Relationships Through Aminoglycoside Block of Mechanotransduction Channels in Lateral Line Hair Cells of Larval Zebrafish.

通过氨基糖苷阻断斑马鱼幼虫侧线毛细胞的机械传导通道来教学剂量-反应关系。

• 发表时间: 2018
• 期刊: Journal of undergraduate neuroscience education : JUNE : a publication of FUN, Faculty for Undergraduate Neuroscience
• 作者: Peterson,HannahPayette;Troconis,EileenL;Ordoobadi,AlexanderJ;Thibodeau-Beganny,Stacey;Trapani,JosefG
• 通讯作者: Trapani,JosefG

Recording Channelrhodopsin-Evoked Field Potentials and Startle Responses from Larval Zebrafish.

• DOI: 10.1007/978-1-0716-0830-2_13
• 发表时间: 2021
• 期刊: Methods in molecular biology
• 作者: Y. Ozdemir;C. A. Hansen;Mohamed Ramy;Eileen L. Troconis;Lauren D McNeil;Josef G. Trapani

A sensation for inflation: initial swim bladder inflation in larval zebrafish is mediated by the mechanosensory lateral line.

膨胀的感觉：斑马鱼幼体的初始鱼鳔膨胀是由机械感觉侧线介导的。

• DOI: 10.1101/2023.01.12.523756
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Venuto,Alexandra;Thibodeau-Beganny,Stacey;Trapani,JosefG;Erickson,Timothy
• 通讯作者: Erickson,Timothy