Circuit dynamics of predictive vocal suppression in auditory cortex

项目总结 在发声过程中，神经系统必须将声音反馈与其他声音分开。做这件事 区别，发声运动相关信号被利用来选择性地抑制听神经元对 声音反馈的可预测声学特征。这种预测性抑制增强了对声音的检测 它与声音反馈同时发生，并且还有助于检测声音错误，这是一个过程 对声乐学习很重要。相比之下，功能失调的抑制被认为会导致听觉 精神分裂症等疾病的幻觉。预见性发声抑制在听觉中的突出作用 通过非侵入性录音，在说话的人类和 发声猴锥体神经元的细胞外记录。然而，细胞决定因素 预测性的发声抑制是未知的，因为猴子和人类的听觉皮质不容易 服从先进的遗传方法，对电路审问有用。虽然我们小组之前发现 小鼠的听觉皮层在发声过程中受到抑制，这些录音是在求偶过程中进行的， 一种以运动、唤醒和嗅觉刺激为特征的状态，所有这些都广泛地抑制 锥体神经元活动。我已经开发了一种新的社交互动模式，在其中我可以监控 对锥体神经元活动进行多光子成像时的发声、运动和唤醒 和小鼠听觉皮质中的中间神经元。我已经将这个范例与声音演示相结合来测试 有声和非有声社会互动中听觉皮质神经元的兴奋性。在目标1中，我将使用 这种方法测量与发声、运动和社会唤醒相关的压抑 检验发声与锥体神经元特异性抑制相对应的假设的相互作用 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，我将系统地从听觉皮质成像 用富含氦气的空气扭曲发声反馈以检验发声假说 抑制是声音反馈的预兆。在目标2.2中，我将测试发声抑制依赖于 从听觉皮层成像探讨发声运动相关信号对中间神经元的强烈激活作用 会发声的先天失聪小鼠。这些实验将测试发声的特异性和预测力。 抑制小鼠的听觉皮质，同时提供其潜在机制的细胞分辨率。 考虑到人类和小鼠听觉皮质的相似组织，我的发现将有助于揭示大脑皮层 影响人类说话过程中声音知觉的回路及其功能障碍 沟通和福祉。

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.