FUNCTIONAL ORGANIZATION OF THE SONG MOTOR CONTROL SYSTEM

描述(由申请人提供)：除了相对简单的有节奏的运动模式外，运动控制模型通常将大部分重点放在端脑上。对于学习的发声行为的产生来说，这当然是正确的，因为脑干主要被视为前脑产生的运动命令的输出路径。除了眼球运动的运动控制之外，关于参与运动输出的脑干核团如何直接影响端脑运动指令的产生，人们知之甚少。这项提案中描述的实验旨在阐明呼吸脑干在歌曲模式生成中的作用，以及更广泛地说，脑干如何影响前脑中运动指令的生成。我们把精力集中在Pam和Dm这两个核团上，这两个核团构成了循环歌唱系统网络中的一个关键环节。它们都接受下行运动通路的直接输入，并通过丘脑中继核Uva的中介，双侧投射回Hvc，这是一个关键的前脑发声控制核团。我们假设，在歌曲的关键转换过程中，这些核团在同步两个半球的运动前活动方面发挥了关键作用。这些实验很重要，因为UVA的病变完全扰乱了歌曲行为，也因为我们几乎完全缺乏对发声呼吸脑干在歌曲模式生成中的功能作用的了解。在第一个目标中，我们建议表征PAM和DM中的神经属性，并评估它们与初级输入和输出结构中的神经元的功能关系。我们将在受约束的睡鸟身上进行这些实验。这允许更大范围的试验性可访问性，例如配对录音。我们将使用几个实验范例，包括刺激诱发发声和歌曲呈现，它们可以“驱动”运动系统，以检查接近发声的条件下的网络特性。在第二个目标中，我们将记录清醒发声鸟类的PAM和DM中的单个神经元，以深入了解它们在发声过程中的发射特性。我们将仔细量化活动模式和声音输出之间的关系。在最终目标中，我们将研究在发声过程中，发声呼吸脑干中神经元的输入-输出网络之间的关系。我们将利用歌曲输出在不同再现中的可变性来告知我们这些不同结构中的每一个在歌曲模式生成中的作用。了解脑干-前脑运动信号的新兴原理以及呼吸系统在发声控制中可能发挥的作用，将有助于深入了解复杂运动行为的神经控制，包括人类言语产生及其病理机制。与公共健康相关的脑干呼吸网络没有很好地整合在发声产生的背景下，因为它们通常被完全视为输出结构。在这项提议中，我们旨在研究脑干到前脑运动信号的性质以及呼吸系统在发声控制中所起的作用。这项工作将提供对复杂运动行为的神经控制的洞察，包括人类语言产生及其病理。

DESCRIPTION (provided by applicant): With the exception of relatively simple rhythmic motor patterns, models of motor control often place most of their emphasis on the telencephalon. This is certainly true for the production of learned vocal behaviors where the brainstem is viewed primarily as an output pathway for motor commands generated in the forebrain. With the recent exception of the motor control of eye movement, little is known about how brainstem nuclei involved in motor output might directly influence the generation of motor commands in the telencephalon. The experiments described in this proposal are aimed at elucidating the role of the respiratory brainstem in song pattern generation and more generally how the brainstem influences motor command generations in the forebrain. We focus our efforts on two nuclei, PAm and DM, which form a critical link in the recurrent song system network. They each receive direct input from the descending motor pathway and projecting bilaterally back to HVC, a key forebrain vocal control nucleus, via the intermediary of the thalamic relay nucleus Uva. We hypothesize that these nuclei play a critical role in synchronizing premotor activity in both hemispheres during key transitions in the song. These experiments are important because Uva lesions completely disrupt song behavior and because of our near complete lack of understanding of the functional role of the vocal-respiratory brainstem in song pattern generation. In the first aim, we propose to characterize neural properties in PAm and DM and evaluate their functional relationship to neurons in their primary input and output structures. We will perform these experiments in restrained sleeping birds. This allows a greater range of experimental accessibility, such as paired recordings. We will use several experimental paradigms, including stimulus-evoked vocalizations and song presentation, that can "drive" the motor system in order to examine network properties under conditions that approach vocal production. In the second aim, we will record from single neurons in both PAm and DM in awake vocalizing birds to gain insight into their firing properties during vocal production. We will carefully quantify the relationship between activity patterns and vocal output. In the final aim, we will investigate the relationship, during vocal production, between input-output networks of neurons in the vocal-respiratory brainstem. We will take advantage of the variability in song output across renditions to inform us about the role of each of these different structures in song pattern generation. Understanding the emerging principles of brainstem-to-forebrain motor signaling and the role the respiratory system might play in vocal control will provide insight into the neural control of complex motor behavior including human speech production and its pathologies PUBLIC HEALTH RELEVANCE Brainstem respiratory networks are not well integrated within the context of vocal production because they are often viewed exclusively as output structures. In this proposal, we aim to investigate the nature of brainstem-to-forebrain motor signaling and the role the respiratory system plays in vocal control. This work will provide insight into the neural control of complex motor behavior, including human speech production and its pathologies.