Neural Circuits Underlying Auditory Processing and Perception of Vocal Sounds

描述(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。在鸣禽和人类的所有发声学习模式中，第一阶段是根据听觉经验形成模板记忆，这些记忆来自于声乐“导师”的声音。一旦形成了导师歌曲的神经表示，这种记忆就会引导感觉-运动整合，因为鸟通过发声和使用听觉反馈来比较它最初的发声和导师的记忆来学习模仿这首歌。鸣禽对导师声音的稳定记忆的存在，最早是在20世纪50年代的S的开创性工作中被证明的，但编码这种记忆表征的神经位点一直难以确定。我们将通过记录单个NCM神经元的活动，并检查它们是否对习得的导师声音产生选择性反应，来检验声音的听觉模板记忆局限于NCM这一较高水平听觉皮质区域的假设。然后，我们将调查神经反应性的经验依赖变化是否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发声学习的听觉模板的基本机制：(目标1)在发声学习的敏感期，NCM神经元是否根据特定的听觉经验对辅导声音进行选择性调谐，从而获得辅导歌曲的表征？如果是这样，那么大脑中的神经活动 NCM神经元群体应该只对习得的导师声音产生强烈的选择性反应。此外，NCM神经元选择性反应的强度应该预测随后模仿导师之歌的能力，阻止模仿学习的细胞信号通路的阻断也应该扰乱选择性神经调谐的发展。(目标2) NCM神经元对发声的选择性神经调谐获得与知觉有何关系？我们将检验这一假设，即NCM神经元中选择性神经调谐的出现不仅基于对导师声音的模板记忆的获得，而且也基于感知地区分学习的声音的能力。总而言之，这项研究将揭示大脑如何编码和记忆听觉声音，以及这些过程如何有助于感知学习的声音的能力的发展进步。鸣禽为实验测试发声学习的细胞和电路机制提供了一个重要的模型，这些机制与人类的听力和沟通障碍有关。这些实验的结果将促进我们对与听觉-声音交流相关的声音对象识别和范畴感知的理解，并使各种听力和交流障碍的治疗方法的发展成为可能。

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.