FUNCTIONAL ORGANIZATION OF THE SONG MOTOR CONTROL SYSTEM

描述（由申请人提供）：除了相对简单的节奏运动模式外，运动控制模型通常将大部分重点放在端脑上。对于习得的发声行为的产生，这当然是正确的，脑干主要被视为前脑产生的运动命令的输出途径。除了最近的眼动运动控制外，关于参与运动输出的脑干核如何直接影响端脑运动命令的产生，我们知之甚少。本实验旨在阐明呼吸脑干在歌曲模式生成中的作用，以及脑干如何影响前脑的运动指令生成。我们重点研究了两个核，PAm和DM，它们构成了循环歌曲系统网络的关键环节。它们各自接受来自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，一个关键的前脑声音控制核。我们假设，在歌曲的关键转换过程中，这些核在同步两个半球的运动前活动方面起着关键作用。这些实验很重要，因为Uva损伤完全破坏了歌唱行为，也因为我们几乎完全缺乏对发声呼吸脑干在歌唱模式产生中的功能作用的理解。在第一个目标中，我们提出表征PAm和DM的神经特性，并评估它们在主要输入和输出结构中与神经元的功能关系。我们将在受限的睡眠鸟类中进行这些实验。这允许更大范围的实验可访问性，如配对录音。我们将使用几个实验范例，包括刺激诱发的发声和歌曲呈现，它们可以“驱动”运动系统，以便在接近声音产生的条件下检查网络特性。在第二个目标中，我们将记录清醒发声鸟类的PAm和DM的单个神经元，以深入了解它们在发声过程中的放电特性。我们将仔细量化活动模式和声音输出之间的关系。在最后的目的中，我们将研究在发声过程中，发声-呼吸脑干神经元的输入-输出网络之间的关系。我们将利用歌曲输出的可变性来告诉我们这些不同结构在歌曲模式生成中的作用。了解脑干到前脑运动信号的新原理以及呼吸系统在声音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，包括人类语言产生及其病理。脑干呼吸网络并没有很好地整合到声音产生的背景下，因为它们通常被视为输出结构。在这个提议中，我们的目的是研究脑干到前脑运动信号的本质和呼吸系统在声音控制中的作用。这项工作将深入了解复杂运动行为的神经控制，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.