Characterizing Secondary Motor Cortical Responses during Sound-Generating Movements

项目总结 听觉皮质对自身产生的声音的抑制--声音是可预测的结果 运动-被认为是在运动过程中检测外部产生的声音的关键。 支持这一假说的人类证据是没有自产生的声音抑制 精神分裂症患者经历幻听并将外部来源归因于内部 声音的感知器。次级运动皮质(M2)到初级听觉皮质(A1)的投射调节 运动过程中的听觉活动，并能够通过兴奋性驱动抑制音调诱发的反应 到A1抑制中间神经元上。这一解剖学和功能证据表明，M2在 依赖经验、特定频率地抑制自身产生的声音。然而，人们对此知之甚少 关于M2在发声运动中的活动，动作和动作之间的联系 感觉的结果是学习的，以及这个回路如何适应不断变化的环境。这一改编- 重新学习运动的声学后果的能力--对于在不断变化的世界中表现至关重要。 这项提议将研究在发声杠杆推动运动中小鼠M2在体内的活动， 具体地说，M2向A1发送了什么信息，以及该信息如何与 该运动的声学结果。目标1将使用光学和电生理技术来比较 在运动过程中M2中听觉和非听觉投射亚群的活动，这产生了 学习到的和预期的声音。目标2，在类似的准备下，然后将评估这些亚群如何 当相同的运动产生意外的声音时作出响应。最后，目标3将使用慢性 钙成像监测M2亚群的反应如何在习得的关联中发展 声音和运动之间的关系，以及活动和/或活跃人口身份在 同样的动作永久地产生新的声音，听觉和运动的联系被重新学习。这个 这些实验的预测是，听觉投射的M2群体代表了预期的 并改变它们的活动，以响应重新学习的听觉后果 有动静。这项工作将描述在变化中从运动到听觉皮质的信息流 声学环境，这是理解听觉-运动系统如何工作所必需的，以及 在处理自身产生的声音的过程中，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.