Determination of the motor patterning system for murine vocalizations with breathing

我们的语音是由有节奏的定时成分组成的，与音节密切相关。这 从鱼到鸣禽再到猴子，整个动物界都保存着特征，这表明 发声中嵌入的节奏是天生编码的。事实上，其他人已经做到了 假设声音产生的节奏性是由大脑中的硬连接神经回路产生的 脑干，但缺乏支持这一理论的证据。 发声是由发音器(喉和舌头)的协同活动产生的。 和呼吸肌。此外，发声必须与甚至是无缝结合在一起。 推翻呼吸节律。考虑到这一点，我们假设，就像其他人一样，如果发声 运动模式系统存在，它将在解剖学和功能上与神经相连 脑干呼吸的回路。我们还假设，同样的电路将 内在地编码发声过程中音节的节奏性。这两个概念-- 自主形成有节奏的行为的能力--将这种神经回路定义为 发声中枢模式生成器‘CPG’，这是同类产品中的第一个。 为了发现这种预测发声的cpg，我们研究了先天的神经控制。 小鼠新生儿的哭声，类似于人类婴儿的哭声。我们发现了那只小鼠 哭声有一个刻板的音节结构和动作程序。先天哭声的这两个特点 建议一个潜在的哭泣CPG。我们发现了一个由几十个脑干组成的新奇的簇 神经元需要执行叫声和前运动到发声中使用的多个肌肉。 在这里，我们试图描述这些神经元的特征，以确定它们是否真的是骨化的 发声CPG。首先，我们将研究这些神经元是否也会产生自主振荡 作为连接，以正确模式的肌肉活动用于发声。然后，我们会 异位激活这些神经元，看看它们是否足以引起哭声。 这项提议的意义是多方面的。首先，我们将确定和 描述一个长期寻求的发声CPG。这构成了绘制全脑地图的基础 先天发声和后天发声中使用的回路。第二，我们将确定发声是如何 和呼吸的CPG相互作用。一个有趣的可能性是，我们最重要的神经回路 呼吸控制可能会被覆盖。事实上，即使不同的哺乳动物CPG合作 产生复杂的行为仍然知之甚少。最终，这项工作将使 自闭症谱系障碍的言语病理机制剖析 失用、构音障碍或口吃。

Our speech is composed of rhythmically timed elements, closely associated with syllables. This feature is conserved across the animal kingdom, from fish to songbirds to monkeys, suggesting that the tempo embedded within vocalizations is innately encoded. Indeed, others have hypothesized that the rhythmicity of sound production is created by hardwired neural circuits in the brainstem, but evidence to support this theory is lacking. Vocalizations are produced by the concerted activity of articulator (laryngeal and tongue) and breathing muscles. Moreover, vocalizations must seamlessly integrate with or perhaps even override the breathing rhythm. Given this, we hypothesized, as have others, that if a vocalization motor patterning system existed, it would be anatomically and functionally connected to the neural circuits for breathing in the brainstem. We also hypothesized that this same circuit would intrinsically encode the rhythmicity of syllables within vocalizations. These two concepts - the ability to autonomously pattern a rhythmic behavior - would define such a neural circuit as a vocalization central pattern generator ‘CPG’, the first of its kind. To discovery this predicted vocalization CPG, we have studied the neural control of innate murine neonatal cries, which are analogous to the cries of human infants. We found that murine cries have a stereotyped syllabic structure and motor program. These two features of innate cries suggest an underlying cry CPG. We have found a novel cluster of several dozen brainstem neurons that are required to execute cries and premotor to multiple muscles used in vocalizations. Here, we seek to characterize these neurons to determine if they are indeed a bonified vocalization CPG. First, we will study if these neurons produce an autonomous oscillation as well as the connectivity to correctly pattern the activity of muscles used in vocalizing. And then, we will ectopically activate these neurons to find out if they are sufficient to elicit cries. The significance of this proposal is multifold. First-and-foremost, we will identify and characterize a long-sought vocalization CPG. This forms a foundation to map the brain-wide circuitry used in innate and learned vocalization. Second, we will determine how the vocalization and breathing CPGs interact. An intriguing possibility is that our most vital neural circuit that controls breathing might be overridden. In fact, even how distinct mammalian CPGs cooperate to produce complex behaviors remains poorly understood. And ultimately, this work will enable dissection of the mechanisms of speech pathologies in autism spectrum disorders as well as apraxia, dysarthria, or stutter.