Neural Circuits Underlying Auditory Processing and Perception of Vocal Sounds

描述（由申请人提供）：鸣禽，像人类一样，在发育的敏感时期学习用于声音交流的特定声音。鸣禽和人类所有的声音学习模型的第一阶段是基于从声音“导师”那里听到的声音的听觉经验的模板记忆的形成。一旦导师歌曲的神经表征形成，这种记忆就会引导感觉运动整合，因为鸟学会通过发声来模仿歌曲，并使用听觉反馈将其初始发声与导师记忆进行比较。鸣禽对导师声音的稳定记忆的存在在20世纪50年代的开创性工作中首次在行为上得到证明，但是对编码这种记忆表征的神经位点的识别一直是难以捉摸的。我们将通过记录单个NCM神经元的活动并检查它们是否对学习到的导师声音产生选择性反应，来检验声乐声音的听觉模板记忆定位于NCM（高级听觉皮层的一个区域）的假设。然后，我们将调查是否经验依赖性的神经反应性的变化也指导感知区分学习的声音的能力的提高。本项目的目的是研究形成声乐学习听觉模板的基本机制：（目的1）NCM神经元是否在声乐学习敏感期根据特定的听觉经验对导师声音进行选择性调谐，从而获得导师歌曲的代表？如果是这样的话， NCM神经元的群体应该只对学习的导师声音产生强烈和选择性的反应。此外，NCM神经元的选择性反应的强度应该预测随后模仿导师歌曲的能力，并且阻断禁止模仿学习的细胞信号传导通路也应该破坏选择性神经调谐的发展。(Aim（二） 在NCM神经元中，对发声的选择性神经调谐的获得是如何与感知相关的？我们将检验这样的假设：NCM神经元中选择性神经调谐的出现不仅是获得导师声音模板记忆的基础，而且是感知区分习得声音的能力的基础。总之，这项研究将揭示大脑如何编码和记忆语音，以及这些过程如何有助于感知学习语音的能力的发展。鸣禽为实验测试与人类听力和交流障碍相关的发声学习的细胞和电路机制提供了一个重要的模型。这些实验的结果将促进我们对声音物体识别和分类感知的理解，并使各种听力和沟通障碍的治疗方法得以发展。

DESCRIPTION (provided by applicant): Songbirds, like humans, learn specific sounds used for vocal communication during a sensitive period of development. The first stage in all models of vocal learning for both songbirds and humans is the formation of a template memory based on auditory experience with sounds heard from vocal "tutors". Once a neural representation of tutor song is formed this memory guides sensorimotor integration as the bird learns to imitate the song by vocalizing and using auditory feedback to compare its incipient vocalizations to that tutor memory. The existence of a stable memory of tutor vocal sounds in songbirds was first demonstrated behaviorally by seminal work in the 1950's, but identification of the neural loci encoding representations of this memory has been elusive. We will test the hypothesis that the auditory template memory of vocal sounds is localized to NCM, a region of higher-level auditory cortex, by recording the activity of individual NCM neurons and examining whether they develop selective responsivity to learned tutor sounds. We will then investigate whether experience-dependent changes in neural responsivity also guide improvements in the ability to perceptually distinguish learned vocal sounds. The aims of this project investigate fundamental mechanisms of forming an auditory template for vocal learning: (Aim 1) Do NCM neurons develop selective tuning to tutor sounds based on specific auditory experience during the sensitive period for vocal learning and thereby acquire a representation of tutor song? If so, then neural activity in a population of NCM neurons should develop a strong and selective response only to learned tutor sounds. Furthermore, the strength of selective responsivity in NCM neurons should predict the subsequent ability to imitate the tutor song, and blockade of cellular signaling pathways that prohibit imitative learning should also disrupt the development of selective neural tuning. (Aim 2) How does the acquisition of selective neural tuning to vocal sounds in NCM neurons relate to perception? We will test the hypothesis that the emergence of selective neural tuning in NCM neurons underlies not only the acquisition of a template memory of tutor sounds, but also the ability to perceptually distinguish learned vocal sounds. In summary, this research will reveal how the brain encodes and remembers auditory-vocal sounds and how such processes contribute to developmental improvements in the ability to perceive learned vocal sounds. Songbirds provide an essential model for experimentally testing cellular and circuit mechanisms of vocal learning that are relevant to hearing and communication disorders in humans. The results of these experiments will advance our understanding of sound object recognition and categorical perception relevant to auditory-vocal communication, and enable the development of treatments for a variety of hearing and communication disorders.