Motor Modulation of Auditory Processing

项目摘要 声音交流依赖于区分我们自己的声音(声音反馈)和其他声音。 发声运动相关的必然放电(发声CD)信号抑制对可预测的听觉反应 声音反馈有助于区分这一点。值得注意的是，人类听觉皮质中的有声CD信号 对语言尤其重要，他们的功能障碍被认为会导致幻听。尽管 有声CD信号的关键角色，监控和控制其活动的挑战 让动物发声阻碍了系统的分析。此应用程序的长期目标是 通过突触、细胞和电路分辨率了解有声CD信号如何调制听觉皮质 对声音反馈的反应，详细了解声音反馈对于理解适应性和适应性不良是必不可少的 试镜的几个方面。我们将获得突触、细胞和回路机制的详细知识 通过研究老鼠这个过程，脊椎动物最适合高级遗传学、电生理学和 光学工具。在之前的资助期间，我们使用这些工具来促进我们对突触和 运动相关CD信号调节听觉皮质活动的电路机制。这些 进展包括将运动映射到听觉皮质回路，确定不同的头部和身体 运动激活了这一通路，以抑制听觉皮质对声音的反应，并表明这一点 帕奇可以“学习”有选择地压制那些可以预测地与运动动作有关的声音。我们 在发声的雄性小鼠中也观察到了听觉皮质的抑制，但在雌性小鼠中发声 求爱，总是伴随着其他运动，以及社会和性刺激。 因此，发声特异的CD信号是否调制听觉皮质并抑制可预测的 声音反馈仍不清楚。幸运的是，我们还开发了光遗传选通超声波的方法 发声(USV)和扭曲声音反馈在隔离的头部固定的小鼠。在此，我们建议 将这些方法与其他最先进的技术相结合，包括体内的多电极阵列 多光子成像，发声相关听觉反馈的受控操作，以及新奇 声学分析的计算方法。在第一个目标中，我们将测试发声的想法 抑制听觉皮质活动，并使用机器学习方法严格量化和比较 自发的和光遗传诱发的紫外线。在第二个目标中，我们将分离大脑皮质对 听觉皮质活动的发声调节。在第三个目标中，我们将扭曲声音反馈以确定是否 听觉皮质的发声抑制是有预测性的，并使用计算方法系统地 量化发声失真。总而言之，这些目标将为突触、细胞和回路提供新的见解 发声CD信号影响听觉皮层处理的机制。

Project Summary Vocal communication depends on distinguishing our own vocal sounds (vocal feedback) from other sounds. Vocal motor-related corollary discharge (vocal CD) signals that suppress auditory responses to predictable vocal feedback help make this distinction. Notably, vocal CD signals in the human auditory cortex are especially important to speech and their dysfunction is thought to cause auditory hallucinations. Despite the key roles postulated for vocal CD signals, the challenges of monitoring and manipulating their activity in vocalizing animals has prevented systematic analyses. The long-term objective of this application is to understand with synaptic, cellular, and circuit resolution how vocal CD signals modulate auditory cortical responses to vocal feedback, detailed knowledge of which is essential to understand adaptive and maladaptive aspects of audition. We will gain detailed knowledge of synaptic, cellular, and circuit mechanisms underlying this process by studying the mouse, the vertebrate most suited to advanced genetic, electrophysiological, and optical tools. In the prior funding period, we used these tools to advance our understanding the synaptic and circuit mechanisms by which movement-related CD signals modulate auditory cortical activity. These advances included mapping a motor to auditory cortical circuit, determining that various head and body movements activate this pathway to suppress auditory cortical responses to sounds, and showing that this pathway can “learn” to selectively suppress sounds that are predictably yoked to locomotor movements. We also observed auditory cortical suppression in vocalizing male mice, but vocalization occurred during female courtship and was always accompanied by other movements, as well as by social and sexual stimuli. Therefore, whether vocalization-specific CD signals modulate the auditory cortex and suppress predictable vocal feedback remain unknown. Fortunately, we also developed methods for optogenetically gating ultrasonic vocalizations (USVs) and for distorting vocal feedback in the isolated, head-fixed mouse. Here we propose to combine these methods with other state of the art techniques, including multi-electrode arrays, in vivo multiphoton imaging, controlled manipulation of vocalization-related auditory feedback, and novel computational methods for voco-acoustic analysis. In the first Aim, we will test the idea that vocalization suppresses auditory cortical activity and use machine learning methods to rigorously quantify and compare spontaneous and optogenetically-evoked USVs. In the second Aim, we will isolate cortical contributions to the vocal modulation of auditory cortical activity. In the third Aim, we will distort vocal feedback to determine if vocal suppression of the auditory cortex is predictive, and use computational methods to systematically quantify vocal distortion. Together, these Aims will provide novel insights into the synaptic, cellular, and circuit mechanisms by which vocal CD signals influence auditory cortical processing.