Neural Mechanisms for Flexible Vocal Communication

灵活语音交流的神经机制

• 批准号: 10658308
• 负责人: ARKARUP BANERJEE
• 金额: $ 211.91万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-03 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658308
• 关键词: Adaptive Behaviors; Animals; Area; Bar Codes; Behavior; Behavioral; Biological; Body Size; Brain; Brain Mapping; Callithrix; Cells; Central America; Chronic; Collaborations; Communication; Communication impairment; Complement; Computer Models; Data; Drosophila genus; Electrophysiology (science); Evolution; Gene Expression; Goals; Health; Human; Individual; Interactive Communication; Lesion; Mammals; Maps; Mastication; Measures; Methods; Molecular; Monitor; Motor; Motor Cortex; Motor output; Movement Disorders; Mus; Neurodevelopmental Disorder; Neurons; Neurosciences; Parkinson Disease; Pattern; Population; Primates; Production; Resolution; Rodent; Rodent Model; Role; Science; Silicon; Slice; Social Environment; Social Interaction; Social Work; Stereotyping; System; Testing; Time; Ultrasonics; Viral; Visual; Work; autism spectrum disorder; comparative; density; experimental study; flexibility; forest; innovation; insight; motor control; motor learning; neural; neural circuit; neuromechanism; neurophysiology; novel; optogenetics; orofacial; response; sensory input; social; social communication; sound; stroke-induced aphasia; virtual; vocal control; vocalization; zebra finch

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.

项目摘要： 是嘲笑笑话还是参加活泼的辩论，我们会灵活地修改我们的语音 在社会背景下。这种适应性行为需要对电动机输出进行实时调整 对快速变化的感觉输入的响应。大脑如何完成这一感觉运动壮举？ 开拓性研究表明，许多人的大脑区域在许多 物种（例如Dropophila，斑马雀，果man，小鼠），但是产生声音的神经回路 灵活性仍然很少理解。人声灵活性，例如在对话中，需要自愿， 与上下文有关声音生产的控制。在哺乳动物中，基于人脑病变，基因 已经提出了表达曲线和一级皮质控制中的神经生理学数据来执行 对声音产生的自愿控制。但是，这个想法的直接证据很少，中立 尤其是在哺乳动物中，尤其是在哺乳动物中的电路级机制仍然未知。 寻找合适的啮齿动物模型将补充初级的先前工作，并将允许 电路级机制要决定。阿尔斯顿的唱歌老鼠（S. Teguina），高度声音啮齿动物 从中美洲的云森林中，非常适合研究灵活的人声行为。歌唱 老鼠表现出显着的人声灵活性，在变量，超声声音之间切换（USV） 并根据社会背景而定义，人为可听的歌曲。相反，大多数啮齿动物 包括实验室小鼠（M. musculus）仅产生USV，尚不知道参与声乐 互动。唱歌的小鼠和实验室小鼠的体型大致相同，大脑切片s。teguina 首先，瞥见与肌肉菌的没有区别。神经电路差异 这种剧烈的行为差异是未知的。在这里，我们建议测试是否能力 唱歌老鼠在社交环境中灵活地应用发声，并且在大多数其他啮齿动物中都缺乏发声 物种取决于运动皮质功能，通过下游声带生产回路起作用。 使用慢性电生理学（AIM 1），单细胞比较连接组学（AIM 2），我们将 确定运动皮层在自然声行为中的作用，并比较皮质连通性 和两个物种之间的功能。在AIM 3中，我们将操纵电路确定其因果关系 在每个物种中的各种人声行为中的作用。通过映射，测量和操纵皮质 圈子，我们将学习运动皮层如何调节社交服务的行为灵活性 沟通。从更广泛的角度来看，这些实验将提供一个系统级别的框架来研究 分层电动机控制电路 - 例如，高级（皮质）控制能够为低水平提供信息 控制器（皮层下模式生成器）生成适当的电动机命令 - 挑战 面对生物和人造药物的面对世界。