Neural Circuits Underlying Auditory Processing and Perception of Vocal Sounds

描述（由申请人提供）：鸣禽和人类一样，在一个敏感的发育时期学习用于声音交流的特定声音。鸣禽和人类的所有声乐学习模式的第一阶段是基于从声乐“导师”那里听到的声音的听觉经验形成模板记忆。一旦形成了对导师之歌的神经表征，这种记忆就会引导感觉运动整合，因为鸟儿会通过发声来学习模仿歌曲，并使用听觉反馈来比较其最初的发声与导师的记忆。在20世纪50年代的开创性工作中，鸣禽对导师声音的稳定记忆的存在首次在行为上得到了证明，但是编码这种记忆表征的神经位点的识别一直难以捉摸。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，来验证声音的听觉模板记忆定位于NCM（一个高级听觉皮层区域）的假设。然后，我们将研究神经反应性的经验依赖变化是否也指导感知区分习得声音的能力的提高。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）在声乐学习的敏感时期，NCM神经元是否根据特定的听觉经验对导师的声音进行选择性调谐，从而获得导师歌曲的表征？如果是这样，那么神经活动

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. PUBLIC HEALTH RELEVANCE: Human infants refine their perceptual abilities during the first several months of life as they form a memory of vocal sounds, and this early phase of perceptual learning is thought to then guide later vocal production. In songbirds, we can directly test cellular mechanisms of processing and remembering vocal sounds in specific neural circuits, which enables us to ask how perceptual refinement is guided by sensory learning at the level of single neurons. These data can only be obtained in an animal model, and are essential in order to develop treatments for disorders of hearing and communication in humans, such as auditory processing disorder and developmental dyslexia in children, as well as developmental disorders characterized by communication deficits such as autism and Tourette's syndrome.