Characterizing Secondary Motor Cortical Responses during Sound-Generating Movements

项目摘要 自发声音的听觉皮层抑制-声音是可预测的结果， 运动-被认为是在运动期间检测外部产生的声音的关键。 支持这一假设的人类证据是， 精神分裂症患者经历幻听并将外部来源归因于内部 感知声音。次级运动皮层（M2）向初级听觉皮层（A1）的投射调节 运动时的听觉活动，并能够通过兴奋性驱动抑制音调诱发反应 到A1抑制性中间神经元上。这一解剖学和功能证据表明，M2在 依赖经验的、特定频率的自发声音抑制。然而， 关于M2在发声运动中的活动，动作和 感觉结果是学习的，以及这种电路如何适应不断变化的环境。这种适应- 重新学习运动的声学结果的能力对于在变化的世界中表现至关重要。 该提议将研究小鼠M2在发声杠杆推动运动期间的体内活动， 具体地说，M2向A1发送什么信息，以及该信息如何与 运动的声学后果。目的1将使用光学和电生理技术进行比较 M2中听觉和非听觉投射亚群在运动期间的活动， 学习和期望的声音。目标2，用类似的准备，然后将评估这些亚群 当同一个动作产生意外的声音时，它会做出反应。最后，目标3将使用慢性 钙成像，以监测M2亚群的反应如何在学习性关联中发展 声音和运动之间的关系，以及活动和/或活动人口身份可能如何变化时， 同样的动作会永久性地产生新的声音，并且大脑-运动的关联会被重新学习。的 从这些实验的预测是，预测M2种群代表预期的 自我产生的声音，并改变他们的活动，以响应重新学习的听觉后果， 运动总之，这项工作将描述信息流从运动到听觉皮层的变化， 声学环境，这对于理解大脑运动系统的功能是必要的， 在处理自己发出的声音时功能障碍也是如此。

PROJECT SUMMARY The auditory cortical suppression of self-generated sounds – sounds that are the predictable consequence of movements – is thought to be critical for the detection of externally generated sounds during movement. Supporting human evidence for this hypothesis is the absence of self-generated sound suppression in Schizophrenia patients who experience auditory hallucinations and attribute an external source to internal percepts of sound. The projections from secondary motor cortex (M2) to primary auditory cortex (A1) modulate auditory activity during movement and are capable of suppressing tone evoked responses via excitatory drive onto A1 inhibitory interneurons. This anatomical and functional evidence points to a putative role of M2 in the experience-dependent, frequency-specific suppression of self-generated sounds. However, little is known about the activity of M2 during sound-generating movements, how an association between action and sensory outcome is learned, and how this circuitry adapts to changing environments. This adaptation – the ability to re-learn the acoustic consequence of a movement – is critical for behaving in a changing world. This proposal will investigate the activity of mouse M2 in vivo during a sound-generating lever push movement, specifically what information M2 sends to A1 and how that information changes in parallel to changes in the acoustic consequence of the movement. Aim 1 will use optical and electrophysiological techniques to compare the activity of auditory and non-auditory projecting subpopulations in M2 during movement that creates a learned and expected sound. Aim 2, with a similar preparation, will then assess how these subpopulations respond when an unexpected sound is generated by the same movement. Finally, Aim 3 will use chronic calcium imaging to monitor how responses of the M2 subpopulations develop across the learned association between sound and movement, and how the activity and/or active population identity might change when the same movement permanently produces a new sound, and the auditory-motor association is re-learned. The predictions from these experiments are that auditory-projecting M2 populations represent the expected self-generated sound and alter their activity in response to re-learning the auditory consequence of movement. Together, this work will describe information flow from motor to auditory cortex in changing acoustic environments, which is necessary for the understanding how the auditory-motor system functions, and so is dysfunctions, in the processing of self-generated sounds.