Encoding of Vocal Signals in the Auditory System

描述(申请人提供)：硬骨鱼外周听觉系统中雌激素依赖性可塑性的发现为建立导致类固醇调节听力的细胞、分子和神经生理学机制提供了理想的模型。雌性军校鱼利用雄性的多谐发声进行配偶定位，并通过支配硬骨鱼主要外周听觉器官球囊的第八神经传入，在雄性嗡嗡声的编码中表现出显著的生殖状态依赖的变化。因此，与非生殖雌性相比，生殖雌性的初级球囊传入信号表现出最佳频率的增加和对雄性哼唱高次谐波的时间编码(通过锁相)精度的提高。无论是17-β-雌二醇还是睾酮治疗3-5周的非生殖雌性，都会诱导生殖雌性的听觉表型增强，这与转录依赖事件一致。观察到的变化可能完全是由于雌激素在生殖女性体内以高出2倍的水平循环。此外，邻近球囊毛细胞层的听觉神经节细胞表达将睾酮转化为雌激素的酶芳香酶，因此可以芳香化循环中的睾酮，以增加局部可获得的雌激素来源。2特定的目标将研究雌激素依赖的分子(钾通道和雌激素受体)和神经生理(毛细胞和初级传入编码)机制的变化，这些机制可以通过听觉系统的相位锁定导致时间处理的改善。拟议的研究还将描述与年龄相关的荷尔蒙状态变化相关的感觉神经可塑性的机制，包括生殖周期中发生的听力变化以及与激素分泌异常模式相关的临床症状(例如特纳氏综合征)。最后，拟议的实验将导致更基本的理解，即声音信号的时间编码缺陷如何依赖于锁相机制，导致在人类包括听神经病/同步障碍患者中观察到的听力障碍。

DESCRIPTION (provided by applicant): The discovery of estrogen-dependent plasticity in the peripheral auditory system of teleost fish provides an ideal model for establishing the cellular, molecular, and neurophysiological mechanisms leading to steroid modulation of audition. Female midshipman fish use the multi-harmonic vocalizations ("hums") of males for mate localization and exhibit dramatic reproductive state-dependent shifts in the encoding of the male's hum by 8th nerve afferents that innervate the saccule, the main peripheral auditory organ in teleosts. Thus, the primary saccular afferents of reproductive females, compared to those of nonreproductive females, show an increase in best frequency and improvement in precision of temporal encoding (via phase-locking) to the upper harmonics of the male hums. Either 17-beta-estradiol or testosterone treatment of non-reproductive females for 3-5 weeks induces the enhanced auditory phenotype of reproductive females, consistent with transcriptionally-dependent events. The observed changes are likely entirely due to estrogen that circulates at 2-fold higher levels in reproductive females. In addition, auditory ganglion cells adjacent to the saccule's hair cell layer express the enzyme aromatase that converts testosterone to estrogen, and can therefore aromatize circulating testosterone to augment the locally available source of estrogen. 2 specific aims will investigate estrogen-dependent shifts in molecular (potassium channels and estrogen receptors) and neurophysiological (hair cell and primary afferent encoding) mechanisms that can lead to improvements in temporal processing via phase-locking in the auditory system. The proposed studies will also delineate mechanisms of sensorineural plasticity that are relevant to shifts in age-related hormonal states, including changes in audition that occur during the reproductive cycle and in clinical syndromes associated with abnormal patterns of hormone secretion (e.g., Turner's Syndrome). Lastly, the proposed experiments will lead to a more fundamental understanding of how deficits in the temporal encoding of acoustic signals, dependent on phase-locking mechanisms, contribute to impairments in hearing observed among humans including those with auditory neuropathy/dys-synchrony.