Motor Modulation of Auditory Processing

描述(申请人提供)：听觉反映的是自我产生的声音，如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，如响亮的汽笛声。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依赖于运动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，但运动皮质对听觉皮质活动的调节被认为对交流所必需的高阶听觉功能是重要的。此外，皮质推论放电机制的功能障碍被推测为精神病患者特有的幻听的基础。尽管它们在正常和紊乱的听力中扮演着假定的角色，但运动和听觉皮质之间相互作用的突触和回路机制仍然是个谜。在这里，我们建议整合小鼠的遗传、突触、电路和行为方法，以绘制将运动相关信号传递到听觉皮质的回路的结构和功能，并测试这些回路在听觉皮质处理中的作用。拟议的实验将描绘皮质回路的结构和功能特性，该回路在自我产生的运动中促进正常的听觉功能，包括发声。这项拟议的研究对NIH任务的意义有四个方面。首先，这项研究可以告知神经系统在自我产生的动作中如何调节正常的听力；这种能力对言语理解和学习至关重要，也是学习和执行包括音乐表演在内的复杂技能的基础。其次，这种运动对大脑皮层的听觉交互作用的功能障碍被认为是驱动 幻听；这种相互作用的突触特征是理解这些病理的起源并最终设计适当的治疗方法的必要步骤。第三，对运动神经回路如何调节听力的理解，可能有助于深入了解如何通过知觉训练或直接操纵神经活动来操纵这些回路，以在听力丧失的情况下促进听觉理解。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，正如这里所提出的，可以提供关于大脑如何对耳聋做出反应的洞察力。

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.