Activity-Dependent Influences on Auditory Circuits

描述（由申请人提供）：拟议研究的总体目标是更好地了解退化的听觉体验对大脑功能的影响，这些变化发生的机制，以及这些知识如何有助于制定有效的补救策略。传导性听力损失（CHL）形式的听力下降，如渗出性中耳炎，是美国儿童中最常见的诊断疾病，并且反复与传导性听力损失解决后持续多年的听觉感知过程缺陷相关。为了更好地理解这些持久的处理缺陷的机制，我们利用了可逆性CHL的技术，允许精确控制发育性听力损失的时间和双侧表达。拟议的实验将涉及历史的CHL的可塑性的单神经元的反应特性和它们的协调安排到功能地图。初步实验将改变CHL发病的年龄，以描绘在下丘，内侧膝状体和初级听觉皮层双耳处理的敏感期调节。持续的研究将比较单侧与双侧CHL对中脑和前脑核团的功能组织的影响，并确定可塑性的方面，持久与那些消失，一旦正常的听力已经恢复。第二条研究路线将提供一个全面的评估经验依赖的影响，单耳和双耳刺激选择性的听觉皮层。这些研究将记录可塑性编码的声音频谱，信噪比，时间包络的变化，以及耳间的水平和时间差的水平上的单个神经元在清醒的动物。通过记录关键的“现实世界”变量，如CHL的时间，CHL的双边模式和CHL的长度无听力影响发展中的中枢听觉系统，这些研究进一步告知医疗保健从业者与儿童CHL的各种干预策略相关的成本和效益。这些实验将进一步加深我们对经验如何塑造大脑功能和行为的理解。拟议的工作将检查经验的指导作用，在形成大脑回路，调解双耳听力。通过结合可逆性传导性听力损失的方法与技术，以表征可塑性的水平上的单个神经元和代表性的地图在听觉中脑和前脑核，拟议的研究介绍了一种有前途的方法来解决基本的研究问题，经验依赖的可塑性和翻译的问题有关的儿童听力损失的病理生理。

DESCRIPTION (provided by applicant): The overall goal of the proposed research is to better understand the impact of degraded auditory experience on brain function, the mechanisms by which these changes occur, and how such knowledge can contribute to the development of effective remediation strategies. Degraded hearing in the form of conductive hearing loss (CHL) such as otitis media with effusion is the most commonly diagnosed illness among children in the United States and has been repeatedly associated with deficits in auditory perceptual processes that persist for years after the conductive loss has been resolved. To better understand the mechanisms underlying these enduring processing deficits, we have utilized a technique for reversible CHL that permits precise control over the timing and bilateral expression of developmental hearing loss. The proposed experiments will relate a history of CHL to plasticity of single neuron response properties and their coordinated arrangement into functional maps. Initial experiments will vary the age of CHL onset to delineate the sensitive period regulation of binaural processing in the inferior colliculus, medial geniculate body and primary auditory cortex. Continuing studies will compare the effects of unilateral versus bilateral CHL on the functional organization of midbrain and forebrain nuclei and identify the aspects of plasticity that endure versus those that fade away once normal hearing has been restored. A second line of research will provide a comprehensive assessment of experience-dependent influences on monaural and binaural stimulus selectivity in the auditory cortex. These studies will document plasticity in the encoding of sound spectra, signal-to-noise ratio, temporal envelope variations as well as interaural level and time differences at the level of the single neuron in the awake animal. By documenting how critical "real-world" variables such as the timing of CHL, the bilateral pattern of CHL and the length of CHL-free hearing impact the developing central auditory system, these studies further inform health care practitioners about the costs and benefits associated with various intervention strategies for childhood CHL. These experiments will further our understanding of how experience shapes brain function and behavior. The proposed work will examine the instructive role of experience in the formation of brain circuits that mediate binaural hearing. By combining a method for reversible conductive hearing loss with techniques to characterize plasticity at the level of single neurons and representational maps in auditory midbrain and forebrain nuclei, the proposed studies introduce a promising approach to address basic research questions regarding experience-dependent plasticity and translational questions related to the pathophysiology of childhood hearing loss.