Midbrain Motor Coding of Vocal Behavior

所有类型的运动动作都依赖于大脑对特定行为的肌肉活动模式的选择和排序。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一种行为。这种包括人类语言在内的非凡行为引出了一个普遍的问题：控制运动的大脑区域是如何使我们能够从一系列可用的行为行动中进行选择的？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的，并且在频率、幅度和持续时间等一小部分容易量化的属性上有所不同。对于不同的大脑区域如何参与发声行为的表现，我们仍然缺乏足够的知识。这对于中脑来说尤其如此，它是大脑半球与后脑和脊髓中的中枢模式产生器之间的关键联系，直接指导肌肉的活动。发出声音的鱼在发出声音的能力上是冠军，这些声音表现出快速、精确的定时声音脉冲。他们还为研究中脑如何控制发声行为提供了高度可处理的模型，这是由于一个具有良好特征和实验可访问的发声中枢模式发生器。该项目将研究中脑在不同发声运动行为的选择、排序和/或模式中的作用。首席研究员将继续从不同背景中招募有才华的学生，包括代表性不足的少数民族，并在行为、神经和分子分析水平上训练他们解决问题。解决声音运动系统如何运作的问题的一个实际方法是识别模型系统，例如鱼类的模型系统，其行为是由易于接近的大脑中心控制的，这些中心与其他脊椎动物的中心具有共同的进化和发育起源。该项目有两个目标，将使用行为、神经生理学和分子方法，首次全面分析一种高度发声鱼类的中脑如何促进发声运动编码和动作选择。目的1将通过免疫组织化学检测即时早期基因（IEG）表达，绘制在不同发声过程中激活的特定中脑群体，IEG是从发声鱼收集的大脑中神经活动增加的代理。目的1还将通过研究与兴奋性和抑制性递质的共表达，以及选择已知调节中脑依赖性发声机制的神经调节剂，来表征eeg识别神经元的神经化学特征。然后，Aim 2将通过结合神经生理学（包括单个神经元记录）和药理学来诱导和调节发声运动活动，研究Aim 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。结果将告诉我们发声机制，更广泛地说，所有脊椎动物群体的运动行为。

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.