Motor Modulation of Auditory Processing

描述（由申请人提供）：听觉感觉反映了自我产生的声音的混合，例如当我们说话或演奏乐器时产生的声音，以及来自其他来源的声音，例如刺耳的警笛声。区分这两类刺激是听觉系统必须克服的主要挑战，以产生稳定的听觉感知并促进听觉引导的行为。来自包括听觉系统在内的各种感觉系统的证据表明，利用运动命令信号的副本以运动依赖的方式调节感觉处理有助于这种区分。虽然这种运动-感觉相互作用在听觉系统中广泛存在，但听觉皮层活动的运动皮层调制被认为对交流所需的高阶听觉功能很重要。此外，皮质必然放电机制的功能障碍被推测为精神病的幻听特征的基础。尽管他们假定在正常和听力障碍的作用，运动和听觉皮层之间的相互作用的突触和电路机制仍然是谜。在这里，我们建议整合遗传，突触，电路和行为的方法在小鼠中映射的结构和功能的电路，将电机相关的信号传递到听觉皮层，并测试这些电路在听觉皮层处理的作用。这项实验将描述在自发运动（包括发声）过程中促进正常听觉功能的皮层回路的结构和功能特性。拟议中的研究对NIH的使命有四方面的意义。首先，这项研究可以告知神经系统如何在自我产生的运动中调节正常的听力;这种能力对言语理解和学习至关重要，也是学习和执行复杂技能的基础，包括音乐表演。第二，在皮层水平上，这种运动与听觉相互作用的功能障碍被认为是 幻听;这种相互作用的突触表征是理解这些病理的起源和最终设计适当疗法的必要步骤。第三，了解运动回路如何调节听力，可以深入了解如何通过感知训练或直接操纵神经活动来操纵这些回路，以促进听力损失时的听觉理解。第四，分析 在没有听力的情况下，这些必然的放电回路的特性，如这里所提出的，可以提供对大脑如何响应耳聋而重组的见解。

DESCRIPTION (provided by applicant): Auditory sensations reflect a mixture of self-generated sounds, such as those created when we speak or play a musical instrument, and sounds arising from other sources, such as a blaring siren. Distinguishing between these two classes of stimuli is a major challenge that the auditory system must overcome to generate stable auditory percepts and facilitate auditory-guided behaviors. Evidence from a wide variety of sensory systems, including the auditory system, indicates that harnessing a copy of a motor command signal to modulate sensory processing in a movement-dependent manner facilitates this distinction. Although such motor-sensory interactions are widespread in the auditory system, motor cortical modulation of auditory cortical activity is thought to be important to higher-order auditory function necessary to communication. Moreover, dysfunction of cortical corollary discharge machinery is speculated to underlie auditory hallucinations characteristic of psychoses. Despite their postulated role in normal and disordered audition, the synaptic and circuit mechanisms underlying interactions between the motor and auditory cortices remain enigmatic. Here we propose to integrate genetic, synaptic, circuit, and behavioral methods in the mouse to map the structure and function of circuits that convey motor-related signals to the auditory cortex and to test the role of these circuits in auditory cortical processing. The propose experiments will delineate the structural and functional properties of cortical circuitry that facilitates normal auditory function during self- generated movements, including vocalization. The significance of the proposed research to the NIH mission is four-fold. First, this research can inform how the nervous system mediates normal hearing during self- generated movements; this ability is essential to speech comprehension and learning, and also is fundamental to the learning and execution of complex skills, including musical performance. Second, dysfunction of this motor to auditory interaction at the cortical level is thought to drive auditory hallucinations; a synaptic characterization of this interaction is a necessary step to understand the genesis of these pathologies and to ultimately design appropriate therapies. Third, an understanding of how motor circuits modulate hearing may provide insights into how these circuits can be manipulated either through perceptual training or direct manipulation of neural activity to facilitate auditory comprehension in the face of hearing loss. Fourth, analyzing the properties of these corollary discharge circuits in the absence of hearing, as also proposed here, can provide insights into how the brain reorganizes in response to deafness.