Encoding of Vocal Signals in the Auditory System

硬骨鱼外周听觉系统雌激素依赖性可塑性的发现 为建立细胞、分子和神经生理学机制提供了理想的模型 导致类固醇调节听力。女见习生鱼用多谐 男性的声音（“嗡嗡声”）的配偶定位和表现出戏剧性的生殖状态- 第八神经传入的男性的嗡嗡声编码的依赖性变化，支配 球囊，硬骨鱼的主要外周听觉器官。因此，初级囊状传入神经 生殖女性，与非生殖女性相比，表现出最好的增加， 频率和提高时间编码的精度（通过锁相）， 男性哼唱的和声要么17岁|3-雌二醇或睾酮治疗非生育女性 持续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。观察到的变化可能完全是由于雌激素， 生殖雌性体内的循环水平高出两倍。此外，听觉神经节细胞 邻近球囊的毛细胞层表达芳香化酶，该酶将testosterone.to 雌激素，因此可以芳香化循环睾酮，以增加局部可用的 雌激素的来源。 两个具体的目标将调查雌激素依赖的分子（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， 可以通过听觉系统中的相位锁定导致时间处理的改善。的 拟议的研究还将阐明与移位相关的感觉神经可塑性机制 与年龄有关的荷尔蒙状态，包括生殖周期中发生的听力变化 并且在与激素分泌的异常模式相关的临床综合征中（例如，特纳的 综合征）..最后，拟议的实验将导致更根本的理解， 声信号的时间编码的缺陷，依赖于锁相机制， 有助于在人类中观察到的听力损伤，包括那些有听觉障碍的人; 神经病变/不同步。'-. '¿......

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 eighth 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 non-reproductive females, show an increase in best frequency and improvement in the precision of temporal encoding (via phase-locking) to the upper harmonics of male hums. Either 17|3-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 two 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. Two 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"associatedwith 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.. '-.'¿......