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.

项目概要： 无论是开怀大笑还是激烈辩论，我们都会根据情况灵活地调整发声方式。 这种适应性行为需要实时调整运动输出。 对快速变化的感觉输入的反应大脑如何完成这种感觉运动壮举？ 开创性的研究已经描述了许多人中负责声音产生的大脑区域的特征。 物种（例如果蝇、斑胸草雀、狨猴、小鼠），但产生声音的神经回路 声音的灵活性仍然知之甚少，例如在谈话中，需要自愿、 在哺乳动物中，基于人类大脑损伤、基因的环境依赖性控制。 根据灵长类动物的表达谱和神经生理学数据，皮层控制被提议发挥作用 然而，这一想法的直接证据很少，而且神经元也很少。 声音灵活性的电路级机制，尤其是哺乳动物的声音灵活性，在很大程度上仍然未知。 寻找合适的啮齿动物模型将补充之前在灵长类动物中的工作，并允许 阿尔斯通的歌唱小鼠（S. teguina）是一种发声高度啮齿类动物，其电路水平机制有待破译。 来自中美洲的云林，非常适合研究灵活的声音行为。 小鼠表现出卓越的声音灵活性，可以在可变的超声波发声（USV）之间切换 相比之下，大多数啮齿类动物都会根据社会背景而定型、人类可听的歌曲。 包括实验室小鼠 (M. musculus) 仅产生 USV，并且不知道参与发声 唱歌小鼠和实验室小鼠的体型大致相同，并且海藻的脑切片也相同。 乍一看与小肌肌的神经回路没有什么区别。 如此剧烈的行为差异是未知的，在这里我们建议测试是否有能力。 唱歌的老鼠可以在社会环境中灵活地发声，而大多数其他啮齿动物则缺乏这种能力 物种，依赖于运动皮层功能，通过下游发声电路起作用。 利用慢性电生理学（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并比较皮层连接性 在目标 3 中，我们将操纵电路来确定它们的因果关系。 通过映射、测量和操纵皮层来了解每个物种的各种声音行为中的作用。 电路，我们将学习运动皮层如何调节行为灵活性以服务于社交 更广泛地说，这些实验将提供一个系统级的研究框架。 分层电机控制电路——例如，高层（皮质）控制如何通知低层 控制器（皮层下模式发生器）生成适当的运动命令——一个挑战 面临着在世界上移动的生物和人工代理。