Hormonal and acoustic regulation of the dopaminergic auditory efferent system: improving detection of social acoustic signals at the level of the inner ear

多巴胺能听觉传出系统的激素和声学调节：改善内耳水平的社会声学信号的检测

• 批准号: 10439364
• 负责人: PAUL M. FORLANO
• 金额: $ 46.2万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439364
• 关键词: Acoustic Trauma; Acoustics; Advertisements; Affect; Aging; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory system; Bass; Behavior; Behavioral; Biological Models; Biological Process; Brain; Brain Diseases; Catecholamines; Cell Nucleus; Cues; Data; Detection; Disease; Dopamine; Dopamine D2 Receptor; Dopamine Receptor; Environment; Exhibits; Exposure to; Female; Fishes; Frequencies; Gene Expression; Gonadal Steroid Hormones; Hair Cells; Hearing; Hormonal; Hormones; Human; Impairment; Incentives; Knowledge; Labyrinth; Link; Measures; Mediating; Melatonin; Metabolism; Mission; Modeling; Parkinson Disease; Partner in relationship; Peripheral; Physiological; Play; Predisposition; Presbycusis; Process; Public Health; Regulation; Research; Rewards; Rodent; Role; Saccule structure; Seasons; Signal Transduction; Stimulus; System; Testing; United States National Institutes of Health; Work; auditory processing; autism spectrum disorder; behavior influence; behavioral response; cholinergic; dopaminergic neuron; excitotoxicity; hearing impairment; human disease; improved; inattention; innovation; insight; male; mesolimbic system; nerve supply; neuromechanism; neuron loss; neurotransmission; noise exposure; normal hearing; novel; receptor expression; reproductive; resilience; response; social; social communication; steroid hormone; vocalization

While there is ample evidence that the dopaminergic inner ear efferent system is upregulated under environmental conditions that induce acoustic trauma, there is a major gap in knowledge about internal regulators of this system and its functional significance under normal hearing conditions, especially in the context of social communication. The overall objective of this application is to determine the hormonal and acoustic signals that underlie the plasticity of dopamine innervation and its synthesis in the inner ear, which, in turn, affects primary auditory processing and encoding of social vocalizations. The plainfin midshipman fish, perhaps the most robust model for this kind of work has the enormous potential of uncovering regulation and function of dopaminergic inner ear efferents in the context of social communication. Importantly, the natural and extraordinary plasticity of the peripheral auditory system (including its dopaminergic efferents) in female midshipman, appears to mirror conditions reflective of human hearing loss and attention. The central hypothesis is that the dopaminergic system of the inner ear is regulated by changes in internal state via circulating hormones and local synthesis of dopamine can be modulated by social acoustic stimuli. This hypothesis, strongly supported by preliminary data, will be tested by the following two specifc aims: 1) Measure hormone-induced changes in dopaminergic neurotransmission and 2) Characterize changes in dopamine synthesis and metabolism after exposure to social acoustic signals. For the first aim circulating levels of sex steroids and melatonin will be experimentally manipulated and changes in dopamine innervation, dopamine receptor gene expression and dopamine synthesis and metabolism in the inner ear will be measured. For the second aim, changes in local dopamine synthesis in the inner ear of females will be measured when exposed to male advertisement calls and when responding and attending to social acoustic stimuli. The proposed project is innovative, in our opinion, because it represents a substantive departure from the status quo by employing a simple but powerful, non-mammalian vertebrate model system where hormone-driven increases in periphery auditory sensitivity enhance encoding of social acoustic signals, and dopamine input to the inner ear plays a role in mediating this change in auditory sensitivity. This contribution will be significant because it will identify physiological and environmental conditions that regulate a novel biological function for dopamine in the peripheral auditory system: increased detection of social-acoustic signals. Importantly, our results could interpret the function of dopamine modulation of the inner ear in a natural and behaviorally relevant context that is absent in mammalian studies thus far. Ultimately, these findings have the potential to provide insights into how cycling (menstrual) or decline in hormones (aging) may be linked to changes in hearing sensitivity and attention as well as brain diseases such as ASD and ADHD where orientation to and detection of social auditory cues is severely impaired.

虽然有足够的证据表明多巴胺能内耳的辐射系统被上调 诱发声学创伤的环境条件，关于内部的知识存在很大的差距 该系统的调节器及其在正常听力条件下的功能意义，尤其是在 社会交流的背景。该应用的总体目的是确定激素和 声学信号是多巴胺神经的可塑性及其在内耳中的合成的基础 转弯，影响社会发声的主要听觉处理和编码。平鳍中部船员鱼， 这类工作中最健壮的模型也许具有揭示监管和的巨大潜力 在社会交流的背景下，多巴胺能内耳出现的功能。重要的是，自然 女性外周听觉系统（包括其多巴胺能产生）的非凡可塑性 中船员似乎反映了反映人类听力损失和关注的条件。中央 假设是内耳的多巴胺能系统受内部状态的变化调节 循环激素和多巴胺的局部合成可以通过社会声学刺激来调节。这 由初步数据强烈支持的假设将通过以下两个特定目的测试：1）测量 激素诱导的多巴胺能神经传递的变化和2）表征多巴胺的变化 暴露于社会声学信号后的合成和代谢。对于第一个目标循环水平 类固醇和褪黑激素将经过实验操纵，多巴胺神经，多巴胺的变化 将测量受体基因表达和多巴胺的合成和代谢。为了 第二个目的，将测量女性内耳中局部多巴胺合成的变化。 男性广告的电话以及回应和参与社会声学刺激时。提议 在我们看来，项目具有创新性，因为它代表了与现状的实质性不同 采用一个简单但功能强大的非哺乳动物脊椎动物模型系统，该模型在该模型中增加了激素驱动的 在外围听觉敏感性中，增强了社会声学信号的编码，多巴胺输入了内心 耳朵在介导这种听觉敏感性的变化中起作用。这项贡献将是重要的，因为它 将确定调节多巴胺生物学功能的生理和环境条件 外围听觉系统：增加社会声学信号的检测。重要的是，我们的结果可能 在自然和行为相关的环境下解释内耳的多巴胺调制的功能 到目前为止，在哺乳动物研究中缺乏。最终，这些发现有可能提供见解 在循环（月经）或激素下降（老化）中如何与听力灵敏度的变化有关 注意以及诸如ASD和ADHD之类的脑部疾病，以此为方向和检测社会疾病 听觉提示严重受损。