Neural Mechanisms for Flexible Vocal Communication

项目摘要： 无论是对一个笑话发笑还是参与一场生动的辩论，我们都会根据自己的声音来灵活地调整发音。 在社会背景下。这种自适应行为需要实时调整运动输出， 对快速变化的感官输入的反应。大脑是如何完成这种感觉运动的壮举的呢？ 开创性的研究已经确定了许多人负责声音产生的大脑区域的特征。 物种（例如，果蝇，斑胸草雀，绒猴，老鼠），但是产生声音的神经回路 人们对灵活性仍然知之甚少。声音的灵活性，例如在谈话中，需要自愿， 对声音产生的上下文相关控制。在哺乳动物中，基于人类大脑病变，基因 表达谱和灵长类动物的神经生理学数据，已经提出皮质控制发挥作用， 对声音产生的意志控制然而，这一想法的直接证据是稀缺的，神经 尤其是在哺乳动物中，发声灵活性背后的回路水平机制在很大程度上仍然未知。 找到一个合适的啮齿动物模型将补充先前在灵长类动物中的工作， 电路级机制被破译。阿尔斯顿的歌唱老鼠（S。teguina），一种声音很大的啮齿动物 来自中美洲的云雾森林，非常适合研究灵活的声音行为。唱歌 小鼠表现出显著的发声灵活性，在变量之间切换，超声波发声（USV） 以及根据社会背景而定的、人类听得见的歌曲。相比之下，大多数啮齿动物 包括实验室小鼠（M. musculus）仅产生USV，并且不知道参与发声 交互.唱歌的老鼠和实验室老鼠的体型大致相同，而S。特吉纳 第一眼看到的是与M.肌肉神经回路差异 这种剧烈行为差异是未知的。在这里，我们建议测试的能力， 唱歌的老鼠在社会环境中灵活地应用发声，而大多数其他啮齿动物缺乏这种能力。 物种，是依赖于运动皮质功能，通过下游发声电路。 使用慢性电生理学（目标1），单细胞比较连接组学（目标2），我们将 确定运动皮层在自然发声行为中的作用， 两个物种之间的关系在目标3中，我们将操纵电路来确定它们的因果关系。 在每个物种的各种发声行为中的作用。通过绘制、测量和操纵大脑皮层 电路，我们将学习如何运动皮层调节行为的灵活性，为社会服务， 通信更广泛地说，这些实验将提供一个系统级的框架来研究 分级电动机控制电路-例如，高水平（皮层）控制如何告知低水平 控制器（皮层下模式发生器），以产生适当的电机命令-一个挑战 面临着生物和人造物质在世界上的移动。

Project Summary: Whether to laugh at a joke or to engage in a lively debate, we flexibly modify our vocalizations based upon social contexts. Such adaptive behavior requires real-time adjustments of motor outputs in response to rapidly changing sensory inputs. How does the brain accomplish this sensorimotor feat? Pioneering studies have characterized the brain areas responsible for sound production in many species (e.g., drosophila, zebra finches, marmosets, mice), but the neural circuits that generate vocal flexibility remain poorly understood. Vocal flexibility, such as during a conversation, requires voluntary, context-dependent control over sound production. In mammals, based on human brain lesions, gene expression profiles, and neurophysiology data in primates, cortical control has been proposed to exert volitional control over sound production. However, direct evidence for this idea is scarce and the neural circuit-level mechanisms underlying vocal flexibility, especially in mammals, remain largely unknown. Finding an appropriate rodent model would complement prior work in the primates and would permit circuit-level mechanisms to be deciphered. Alston’s singing mice (S. teguina), a highly vocal rodent from the cloud forests of Central America, are ideally suited to study flexible vocal behaviors. Singing mice show remarkable vocal flexibility, switching between variable, ultrasonic vocalizations (USVs) and stereotyped, human-audible songs depending upon social context. In contrast, most rodents including lab mice (M. musculus) produce only USVs and are not known to participate in vocal interactions. Singing mice and lab mice are roughly the same body size, and brain slices of S. teguina at a first glimpse is indistinguishable from those of M. musculus. Neural circuit differences underlying such drastic behavioral divergence are unknown. Here we propose to test whether the ability of the singing mice to apply vocalizations flexibly within a social context, and lack thereof in most other rodent species, is dependent upon motor cortical function, acting via downstream vocal production circuits. Using chronic electrophysiology (Aim 1), single-cell comparative connectomics (Aim 2), we will determine the role of motor cortex during natural vocal behaviors and compare cortical connectivity and function between two species. In Aim 3, we will manipulate the circuit to determine their causal role in various vocal behaviors in each species. By mapping, measuring and manipulating cortical circuits, we will learn how motor cortex modulates behavioral flexibility in service of social communication. More broadly, these experiments will provide a systems-level framework to study hierarchical motor control circuits – for e.g., how high-level (cortical) control can inform low-level controllers (subcortical pattern-generators) to generate appropriate motor commands – a challenge faced by biological and artificial agents moving through the world.