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，然而对于神经系统如何学习控制复杂的肌肉动作所知甚少。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，它提供了一种独特的系统来实现这一目标，因为它获得鸣叫的方式与我们学习许多运动技能（包括语言）的方式非常相似。目的：我们的建议旨在通过记录自由行为的幼斑胸草雀在整个鸣叫学习过程中的运动皮质模拟结构（核RA）中的神经元来描述鸣叫的运动程序是如何发展的（目的1）。RA被广泛认为是声音学习的场所，它接收来自高阶运动区HVC和基底神经节回路的收敛输入。该提案将研究这两种输入在学习期间形成RA运动命令中的各自作用（目的2）。我们研究了基于听觉反馈的表现评估，这是歌曲学习和歌曲维持的关键因素，如何影响运动程序的发展（目的3）。最后，我们评估了学习诱导的RA运动程序变化在多大程度上是由HVC（其前运动输入）的变化驱动的（目的4）。方法：该提案将结合强大的方法来研究这些问题：定制的机动微驱动器将允许记录歌唱的幼鸟RA中的单个神经元，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，将我们的观察结果整合到一个生物物理上合理的歌唱回路如何学习和运作的模型中。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进化的，以及在学习方面，运动回路是如何组织起来的。鸣禽和人类产生发声的神经回路之间有许多同源性和相似性，因此我们的发现也将讨论如何获得语言和其他习得运动行为的运动程序。了解复杂运动学习的神经关联将使我们能够确定该过程可能失败的原因，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.