Circuit dynamics of predictive vocal suppression in auditory cortex

听觉皮层预测性声音抑制的电路动力学

• 批准号: 10523049
• 负责人: Thomas Curtis Harmon
• 金额: $ 7.61万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10523049
• 关键词: Acoustics; Affect; Air; Arousal; Auditory; Auditory Hallucination; Auditory area; Auditory system; Behavioral; Communication; Courtship; Detection; Disease; Dissociation; Feedback; Frequencies; Functional disorder; Genetic; Genetic Techniques; Head; Hearing; Helium; Human; Image; Interneurons; Locomotion; Measures; Mediating; Methods; Monitor; Monkeys; Motor; Mus; Nervous System; Neurons; Organism; Perception; Personal Satisfaction; Physiological; Population; Process; Production; Resolution; Schizophrenia; Shapes; Signal Transduction; Social Interaction; Social isolation; Specificity; Speech; Stimulus; Testing; Voice; congenital deafness; excitatory neuron; experimental study; extracellular; genetic approach; hippocampal pyramidal neuron; in vivo; inhibitory neuron; innovation; male; multiphoton imaging; neural; neural circuit; neuromechanism; non-verbal; novel; response; social communication; sound; two-photon; vocal learning; vocalization

Project summary During vocalization, the nervous system must dissociate vocal feedback from other sounds. To make this distinction, vocal motor-related signals are harnessed to selectively suppress responses of auditory neurons to predictable acoustic features of vocal feedback. This predictive suppression enhances the detection of sounds that occur simultaneously with vocal feedback and also facilitates the detection of vocal errors, a process important to vocal learning. In contrast, dysfunctional suppression is thought to give rise to auditory hallucinations in disorders like schizophrenia. The prominence of predictive vocal suppression in the auditory cortex has been most thoroughly demonstrated with noninvasive recordings in speaking humans and extracellular recordings from pyramidal neurons in vocalizing monkeys. However, the cellular determinants of predictive vocal suppression are unknown because the auditory cortex of monkeys and humans is not readily amenable to advanced genetic methods useful for circuit interrogation. While our group previously found that mouse auditory cortex was suppressed during vocalization, these recordings were conducted during courtship, a state that also features locomotion, arousal, and olfactory stimulation, all of which broadly suppress pyramidal neuron activity. I have developed a novel social interaction paradigm in which I can monitor vocalizations, locomotion, and arousal while conducting multiphoton imaging the activity of pyramidal neurons and interneurons in the mouse auditory cortex. I have combined this paradigm with sound presentations to test the excitability of auditory cortical neurons during vocal and non-vocal social interactions. In Aim 1, I will use this approach to measure suppression related to vocalization, locomotion, and arousal during social interactions to test the hypothesis that vocalization corresponds with specific suppression of pyramidal neurons that respond to vocal feedback and activation of certain interneurons, while non-vocal facets of courtship suppress a broader population of neurons. In Aim 2.1, I will image from the auditory cortex while systematically distorting vocal feedback with air enriched with gradations of helium to test the hypothesis that vocal suppression is predictive of vocal feedback. In Aim 2.2, I will test the hypothesis that vocal suppression relies on strong activation of interneurons by vocal motor-related signals by imaging from the auditory cortex of vocalizing, congenitally deaf mice. These experiments will test the specificity and predictive power of vocal suppression in the mouse auditory cortex while providing cellular resolution of its underlying mechanisms. Given the similar organization of the human and mouse auditory cortex, my findings will shed light on cortical circuits that influence vocal perception during human speech and whose dysfunction interferes with communication and well-being.

项目摘要 在发声过程中，神经系统必须将声音反馈与其他声音分离。做这个 区分，声带相关的信号被利用以选择性地抑制听觉神经元对 人声反馈的可预测声特征。这种预测性抑制增强了声音的检测 这与人声反馈同时发生，还促进了人声错误的检测 对声乐学习很重要。相比之下，可以认为功能失调的抑制会引起听觉 精神分裂症等疾病的幻觉。听觉中预测性声抑制的突出性 皮质在说话的人类和 来自锥体神经元的细胞外记录。但是， 预测性声抑制是未知的，因为猴子和人类的听觉皮层不容易 适用于晚期遗传学方法，可用于电路询问。虽然我们的小组以前发现 鼠标听觉皮层在发声过程中被抑制，这些录音是在求爱期间进行的 也具有运动，唤醒和嗅觉刺激的状态，所有这些状态都广泛抑制 锥体神经元活性。我已经开发了一种新颖的社交互动范式，可以在其中监视 进行多光子成像时，发声，运动和唤醒是锥体神经元的活性 和鼠标听觉皮层中的中间神经元。我已经将这个范式与声音演示进行了测试 声音和非声音社交互动过程中听觉皮质神经元的兴奋性。在AIM 1中，我会使用 这种测量与发声，运动和唤醒有关的抑制的方法 相互作用以检验发声与锥体神经元的特异性抑制相对应的假设 响应声音反馈和某些中间神经元的激活，而求爱方面的方面 抑制更广泛的神经元。在AIM 2.1中，我将从听觉皮层中进行映像，同时 扭曲声音反馈，充满氦等级的空气来检验声音的假设 抑制是人声反馈的预测。在AIM 2.2中，我将测试人声抑制的假设 通过从听觉皮层成像的声带相关信号对中间神经元的强烈激活 发声，先天性聋子。这些实验将测试声乐的特异性和预测能力 在提供其潜在机制的细胞分辨率的同时，在小鼠听觉皮层中抑制。 鉴于人类和鼠标听觉皮层的类似组织，我的发现会揭示皮质 影响人类言语期间发声的电路，其功能障碍会干扰 沟通和福祉。