Midbrain Motor Coding of Vocal Behavior

所有类别的运动动作都依赖于大脑来选择和排序特定于行为的肌肉活动模式。这包括发声，这是鱼类、两栖动物、爬行动物、鸟类和哺乳动物共有的行为。这种包括人类言语在内的非凡行为引出了一个普遍问题：控制运动的大脑区域如何成为我们从可用行为动作菜单中进行选择的能力的基础？声音行为是回答这个问题的绝佳模型，因为它们通常是高度刻板化的，并且在一小部分易于量化的属性（例如频率、幅度和持续时间）方面存在差异。对于不同的大脑区域如何参与声音行为的表现，人们仍然缺乏了解。对于中脑来说尤其如此，它在大脑半球和后脑和脊髓中发现的中央模式发生器之间提供了关键的联系，直接指导肌肉的活动。发声鱼是发声能力的冠军，这些发声表现出快速、精确定时的声音脉冲。他们还提供了高度易于处理的模型，用于研究中脑如何通过良好表征且可通过实验访问的声音中枢模式生成器来控制声音行为。该项目将研究中脑在不同声音运动行为的选择、排序和/或模式中的作用。首席研究员将继续招募来自不同背景的优秀学生，包括代表性不足的少数群体，并训练他们在行为、神经和分子分析水平上解决问题。解决发声运动系统如何运作问题的一种实用方法是识别模型系统，例如鱼类的系统，其中行为由易于访问的大脑中心控制，这些大脑中心与其他脊椎动物的中心共享进化和发育起源。该项目有两个目标，即利用行为、神经生理学和分子方法，首次全面分析高发声鱼类的中脑如何促进发声运动编码和动作选择。目标 1 将通过使用免疫组织化学检测从发声鱼收集的大脑中立即早期基因 (IEG) 的表达（神经活动增加的代表）来绘制不同发声期间激活的特定中脑群体的图谱。目标 1 还将通过研究兴奋性和抑制性递质的共表达来表征 IEG 识别的神经元的神经化学特征，并选择已知可调节中脑依赖性发声机制的神经调节剂。 然后，目标 2 将通过将神经生理学（包括单神经元记录）与药理学相结合来诱导和调节发声运动活动，研究目标 1 中确定的中脑神经元群在发声行为的选择、排序和/或模式中的作用。研究结果将告诉我们有关所有脊椎动物群体的发声机制以及更广泛的运动行为的信息。

All classes of motor actions depend on the brain for selecting and sequencing behavior-specific muscle activity patterns. This includes vocalization, a behavior that is shared among fishes, amphibians, reptiles, birds and mammals. This remarkable behavior that includes human speech begs the general question: How do brain regions that control movement underlie our ability to select from a menu of available behavioral actions? Vocal behaviors are excellent models for answering this question because they are often highly stereotyped and differ in a small set of easily quantified properties such as frequency, amplitude and duration. There remains an astonishing lack of knowledge of how different brain regions participate in the performance of vocal behavior. This is especially the case for the midbrain that provides a key link between the cerebral hemispheres and central pattern generators found in the hindbrain and spinal cord that directly instruct the activity of muscles. Sound producing fish are champions in the ability to generate vocalizations that exhibit rapid, precisely timed sound pulses. They also provide highly tractable models for studying how the midbrain controls vocal behavior due to a well-characterized and experimentally accessible vocal central pattern generator. The project will investigate the role of the midbrain in the selection, sequencing and/or patterning of different vocal motor behaviors. The Principal Investigator will continue to recruit a talented population of students from diverse backgrounds, including under-represented minorities, and train them in problem-solving at behavioral, neural and molecular levels of analysis.A practical way to address questions of how vocal motor systems function is to identify model systems, such as those in fish, where behavior is controlled by readily accessible brain centers that share evolutionary and developmental origins with centers in other vertebrates. This project has two aims that will use behavioral, neurophysiological and molecular methods to provide the first comprehensive analysis of how the midbrain of a highly species of vocal fish contributes to vocal motor coding and action selection. Aim 1 will map specific midbrain populations activated during different vocalizations by using immunohistochemistry to detect immediate early gene (IEG) expression, a proxy for increased neural activity, in brains collected from vocalizing fish. Aim 1 will also characterize the neurochemical signature of IEG-identified neurons by investigating co-expression with excitatory and inhibitory transmitters and select neuromodulators that are known to modulate midbrain-dependent mechanisms of vocalization. Aim 2 will then investigate the role of midbrain neuronal populations identified in Aim 1 in the selection, sequencing and/or patterning of vocal behavior by combining neurophysiology, including single neuron recording, with pharmacology to induce and modulate vocal motor activity. The results will inform us about vocal mechanisms and, more broadly, motor behaviors among all groups of vertebrates.