Neural mechanisms underlying vocal learning in the songbird

描述（由申请人提供）：习得的运动序列是大多数人类交流的基础，但对神经系统如何学习控制所涉及的复杂肌肉动作知之甚少。我们的长期目标是描述习得运动行为的神经回路机制。斑胸草雀是一种鸣禽，它提供了一个独特的系统来实现这一目标，因为它获得歌声的方式与我们学习许多运动技能（包括语言）的方式大致相同。目的：我们的建议的目的是描述如何记录从神经元的运动皮层模拟结构（核RA）在自由行为，青少年斑胸草雀在整个歌曲学习（目标1）的运动程序的歌曲发展。RA被广泛认为是发声学习的场所，RA接收来自高阶运动区（HVC）和基底神经节回路的会聚输入。该提案将研究这两个输入在学习过程中塑造RA运动命令的各自作用（目标2）。我们研究如何听觉反馈为基础的性能评价，歌曲学习和歌曲维护的一个重要组成部分，影响运动程序的发展（目标3）。最后，我们评估在何种程度上的学习引起的RA运动程序的变化是由HVC的变化，其运动前输入（目的4）。研究方法：该提案将结合强大的方法来研究这些问题：定制的电动微驱动器将允许记录唱歌的幼年鸟中RA中的单个神经元，并且长期植入的反向微透析装置将使基底神经节回路的快速和可逆失活成为可能。最后，我们将使用数学模型，将我们的观察结果纳入一个关于歌曲回路如何学习和运作的生物物理学合理模型。公共卫生相关性我们的实验旨在描述复杂运动行为背后的运动程序是如何演变的，以及运动回路在学习方面的组织逻辑。鸣禽和人类产生发声的神经回路之间的同源性和相似性很多，因此我们的研究结果也将涉及如何获得语言和其他学习运动行为的运动程序的问题。了解复杂运动学习的神经相关性将使我们能够确定该过程如何失败，从而解决各种运动障碍和残疾的可能原因。

DESCRIPTION (provided by applicant): Learned motor sequences underlie most of human communication, yet remarkably little is known about how the nervous system learns to control the complex muscle actions involved. Our long term goal is to describe the neural circuit mechanisms underlying the acquisition of learned motor behaviors. The zebra finch, a songbird, provides a unique system in which to pursue this goal, as it acquires its song in much the same way that we learn many of our motor skills, including speech. Aims: Our proposal aims to describe how the motor program for song develops by recording from neurons in a motor cortex analogue structure (nucleus RA) in the freely behaving, juvenile zebra finch throughout song learning (Aim 1). Widely thought to be the site of vocal learning, RA receives convergent input from a higher order motor area, HVC, and from a basal ganglia circuit. The proposal will examine the respective roles of these two inputs in shaping the motor command in RA during learning (Aim 2). We examine how auditory feedback-based performance evaluation, a crucial ingredient for both song learning and song maintenance, influences the development of the motor program (Aim 3). Lastly, we assess the extent to which the learning induced changes in the RA motor program are driven by changes in HVC, its premotor input (Aim 4). Methods: The proposal will examine these issues with a combination of powerful methods: custom- made motorized microdrives will allow the recording of single neurons in RA in the singing, juvenile bird, and a chronically implanted reverse microdialysis device will make possible the fast and reversible inactivation of the basal ganglia circuit. Finally, we will use mathematical models that incorporate our observations into a biophysically plausible model of how the song circuit learns and functions. PUBLIC HEALTH RELEVANCE Our experiments aim to describe how the motor program underlying a complex motor behavior evolves, and the logic by which the motor circuits underlying it are organized with respect to learning. The homologies and analogies between the neural circuits generating vocalizations in songbirds and humans are many, thus our findings will also speak to the question of how the motor program underlying speech and other learned motor behaviors may be acquired. Understanding the neural correlates of complex motor learning will allow us to pinpoint how the process may fail, thus addressing the possible causes of various motor disorders and disabilities.