The Neural Correlates and Mechanisms of Spatial Stream Segregation in Rat Primary

大鼠初级空间流分离的神经关联和机制

• 批准号: 8459311
• 负责人: Justin Daniel Yao
• 金额: $ 3.58万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8459311
• 关键词: Accounting; Auditory; Auditory area; Brain; Cells; Characteristics; Cochlear Implants; Complex; Computer Simulation; Contralateral; Data; Exhibits; Experimental Models; Felis catus; Future; GABA Antagonists; Goals; Hearing; Hearing Aids; Human; Inherited; Interneurons; Ipsilateral; Laboratories; Location; Mediating; Methods; Modeling; Modification; Neurons; Neurosciences; Noise; Process; Property; Psychophysics; Rattus; Research; Rodent; Role; Sampling; Scheme; Source; Stimulus; Stream; Techniques; Testing; Time; Whole-Cell Recordings; base; design; extracellular; in vivo; innovation; interest; neuromechanism; public health relevance; receptive field; receptor; relating to nervous system; research study; response; segregation; sound

DESCRIPTION (provided by applicant): In a complex auditory scene, a listener is confronted with multiple interleaved sequences of sounds that must somehow be assigned to corresponding sound sources. This process is referred to as "stream segregation", where each "stream" represents the perceptual correlate of a sound sequence from a particular source. Spatial separation of sound sources facilitates the recognition of multiple sequences of sounds (i.e., multiple "streams") as belonging to distinct sources. A central question in auditory neuroscience is how auditory streams are formed in the brain. The goal of this proposal is to further explore the cortical correlates of spatial stream segregation, as well as uncover their cellular mechanisms. While cats have been favored as experimental models for spatial hearing research, they are impractical for in vivo intracellular and pharmacological experiments. Instead, small rodents like the rat are well-suited for these kinds of studies. Thus, we have chosen the rat, rather than the cat, as a model for the proposed research. In order to achieve the goal of elucidating the cellular mechanisms of spatial stream segregation, we propose three specific aims: 1) Evaluate the spatial sensitivity of rat primary auditory cortex (A1); 2) Characterize spatial stream segregation in rat A1; 3) Determine the neural mechanisms of spatial stream segregation in rat A1. Aim 1 will utilize extracellular techniques to assess the spatial sensitivit of rat A1 units to noise burst stimuli presented from free-field speaker locations that vary 360-deg across azimuth. Aim 2 will implement a spatial stream segregation paradigm adapted from a previous psychophysical study performed in our lab. Cortical responses will be recorded with extracellular techniques and analyzed with innovative methods and computational models. Aim 3 will combine extracellular recordings with the pharmacological blockade of GABAA receptors to determine the role of intra-cortical inhibition in spatial stream segregation. This proposal wil investigate, for the first time, whether the intra-cortical inhibitory effects by GABAA receptors account for spatial stream segregation in A1. Our examination of the potential intra-cortical mechanisms that may take part in the formation of auditory streams will advance our understanding of how auditory scene analysis is accomplished in A1. Specifically, which characteristics are synthesized de novo in the cortex, enhanced by cortical processing, or passively inherited from subcortical inputs? Elucidating mechanisms responsible for various aspects of spatial stream segregation have broad implications in aiding the design of sound processing schemes for enhanced hearing in complex auditory scenes by users of hearing aids and cochlear implants.

描述（由申请人提供）：在复杂的听觉场景中，收听者面对必须以某种方式分配给对应声源的多个交错的声音序列。这个过程被称为“流分离”，其中每个“流”表示来自特定源的声音序列的感知相关性。声源的空间分离便于识别多个声音序列（即，多个“流”）属于不同的源。听觉神经科学的一个中心问题是听觉流是如何在大脑中形成的。本研究的目的是进一步探索空间流分离的皮层相关性，并揭示其细胞机制。虽然猫已被青睐的空间听觉研究的实验模型，他们是不切实际的体内细胞内和药理学实验。相反，像老鼠这样的小型啮齿动物非常适合这类研究。因此，我们选择了大鼠而不是猫作为拟议研究的模型。为了阐明空间流分离的细胞机制，我们提出了三个具体目标：1）评价大鼠初级听皮层（A1）的空间敏感性; 2）表征大鼠A1的空间流分离; 3）确定大鼠A1空间流分离的神经机制。目的1将利用细胞外技术来评估大鼠A1单位的空间敏感性，以噪声突发刺激从自由场扬声器的位置，变化360度的方位角。目标2将实现一个空间流分离范式，改编自我们实验室以前进行的心理物理研究。皮质反应将记录与细胞外技术和分析与创新的方法和计算模型。目的3将联合收割机结合细胞外记录和GABAA受体的药物阻断来确定皮层内抑制在空间流分离中的作用。这一建议将调查，第一次，是否皮层内的抑制作用GABAA受体占空间流分离A1。我们的检查可能参与听觉流的形成的潜在的皮层内机制，将推进我们的理解，听觉场景分析是如何在A1完成的。具体来说，哪些特征是在皮层中重新合成的，哪些特征是通过皮层处理得到增强的，哪些特征是从皮层下输入中被动遗传的？阐明负责空间流分离的各个方面的机制在帮助助听器和耳蜗植入物的用户设计用于在复杂听觉场景中增强听力的声音处理方案方面具有广泛的意义。