Circuit dynamics of predictive vocal suppression in auditory cortex

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。让这个 区别，发声运动相关的信号被利用来选择性地抑制听觉神经元对 声音反馈的可预测的声学特征。这种预测性抑制增强了声音的检测 与声音反馈同时发生，也便于检测声音错误， 对声乐学习很重要。相反，功能失调的抑制被认为会引起听觉 精神分裂症等疾病中的幻觉听觉系统中预测性发声抑制的显著性 在人类说话的过程中，无创记录最彻底地证明了大脑皮层， 发声猴锥体神经元的细胞外记录。然而，细胞的决定因素 预测性声音抑制是未知的，因为猴子和人类的听觉皮层不容易 适用于电路询问的先进遗传方法。虽然我们的团队之前发现， 小鼠听觉皮层在发声过程中受到抑制，这些记录在求偶期间进行， 这种状态也具有运动、唤醒和嗅觉刺激的特征，所有这些都广泛地抑制了 锥体神经元活动我发明了一种新的社会互动模式， 在进行锥体神经元活动的多光子成像时， 和小鼠听觉皮层的中间神经元我将这个范例与声音演示结合起来， 声音和非声音社交互动期间听觉皮质神经元的兴奋性。在目标1中，我将使用 这种方法可以测量与社交过程中的发声、运动和唤醒相关的抑制， 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 对声音反馈和某些中间神经元的激活做出反应，而求爱的非声音方面 抑制更广泛的神经元群体。在目标2.1中，我将从听觉皮层成像，同时系统地 用富含氦气的空气来扭曲声音反馈，以测试声音反馈的假设。 抑制是声音反馈的预测。在目标2.2中，我将检验发声抑制依赖于 通过听觉皮层的成像， 会发声的先天性耳聋小鼠这些实验将测试声音的特异性和预测能力， 抑制小鼠听觉皮层，同时提供其潜在机制的细胞分辨率。 考虑到人类和老鼠听觉皮层的相似结构，我的发现将有助于阐明大脑皮层的 在人类讲话过程中影响声音感知的回路，其功能障碍干扰 沟通和幸福。

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.