Characterizing Secondary Motor Cortical Responses during Sound-Generating Movements

表征发声运动期间的次级运动皮层反应

• 批准号: 10472013
• 负责人: Brooke E Holey
• 金额: $ 3.85万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-04 至 2023-09-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10472013
• 关键词: Acoustics; Anatomy; Animals; Auditory; Auditory Hallucination; Auditory area; Behavior; Calcium; Cells; Chronic; Code; Communication; Detection; Electrophysiology (science); Environment; Forelimb; Frequencies; Functional disorder; Goals; Hearing problem; Human; Image; Interneurons; Label; Learning; Mental disorders; Modality; Monitor; Motor; Motor Cortex; Motor Neurons; Movement; Mus; Neurons; Optics; Outcome; Patients; Population; Preparation; Probability; Process; Randomized; Rhodopsin; Role; Schizophrenia; Sensory; Shapes; Signal Transduction; Source; System; Techniques; Training; Transgenic Mice; Update; Viral; Work; calmodulin-dependent protein kinase II; expectation; experience; experimental study; extracellular; in vivo; inhibitory neuron; motor disorder; network dysfunction; novel; relating to nervous system; response; sound

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.

项目摘要 听觉的皮质抑制自我生成的声音 - 声音是可预测的结果 运动 - 被认为对于在运动过程中检测外部产生的声音至关重要。 支持人类证据的这一假设是没有自我生成的声音抑制 经历听觉幻觉并将外部来源归因于内部的精神分裂症患者 声音的感知。从二级运动皮层（M2）到主听觉皮层（A1）调节的项目 运动过程中的听觉活动，能够通过兴奋驱动来抑制诱发的响应 进入A1抑制性中间神经元。该解剖学和功能证据表明M2在 与经验有关的，特定于频率的自我生成声音的抑制。但是，鲜为人知 关于M2在发出声音运动过程中的活动，动作与行动之间的关联 学习感觉结果，以及该电路如何适应不断变化的环境。这种适应 - 重新学习运动后果的能力 - 对于在不断变化的世界中行事至关重要。 该建议将调查小鼠M2在发出声音杆的推动运动过程中的活性， 特别是M2发送到A1的信息，以及该信息如何与变化并行变化 运动的声音后果。 AIM 1将使用光学和电生理技术进行比较 在运动过程中，M2中听觉和非审计人投影亚群的活动创造了一个 学会和预期的声音。 AIM 2进行类似的准备，然后将评估这些亚群 当同一动作产生意外的声音时做出响应。最后，AIM 3将使用慢性 钙成像以监视M2亚群的响应如何在学习的整个关联中发展 在声音和运动之间，以及活动和/或活动人口身份可能会发生变化 同样的运动永久产生新的声音，并重新学习了听觉运动协会。 这些实验的预测是，听觉项目的M2群体代表了预期的 自我生成的声音并因重新学习的听觉后果而改变其活动 移动。这项工作将描述从电动机到听觉皮层的信息流程。 声学环境，这是了解听觉运动系统如何功能的必要条件，并且 功能障碍在处理自我生成的声音中也是如此。