Encoding of Vocal Signals in the Auditory System

描述（由申请人提供）：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觉的细胞、分子和神经生理机制提供了理想模型。女性见习生鱼使用的多谐波发声（“嗡嗡声”）的男性配偶本地化，并表现出显着的生殖状态依赖的转变，在编码的男性的嗡嗡声由第8神经传入，支配球囊，在硬骨鱼的主要外周听觉器官。因此，初级囊状传入的生殖女性相比，nonreproductive女性，显示出最佳频率的增加和改善的精度的时间编码（通过锁相）的男性嗡嗡声的上谐波。17-β-雌二醇或睾酮治疗非生殖雌性3-5周诱导生殖雌性的增强的听觉表型，与转录依赖性事件一致。观察到的变化可能完全是由于雌激素在生殖女性中以2倍高的水平循环。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芳香化酶，因此可以使循环睾酮芳香化，以增加局部可用的雌激素来源。2个具体目标将研究分子（钾通道和雌激素受体）和神经生理学（毛细胞和初级传入编码）机制中的雌激素依赖性变化，这些机制可以通过听觉系统中的锁相改善时间处理。拟议的研究还将描述与年龄相关的激素状态变化相关的感觉神经可塑性机制，包括生殖周期期间发生的听力变化和与激素分泌异常模式相关的临床综合征（例如，Turner综合征）。最后，拟议的实验将导致更根本的理解，如何赤字的时间编码的声信号，依赖于锁相机制，有助于听力障碍的人类之间观察到的，包括那些与听觉神经病变/不同步。

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.