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

描述(申请人提供)：在复杂的听觉场景中，听众面对的是多个交错的声音序列，这些声音必须以某种方式分配给相应的声源。这个过程被称为“流分离”，其中每个“流”代表来自特定来源的声音序列的知觉关联。声源的空间分离便于将多个声音序列(即，多个流)识别为属于不同的源。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。这项建议的目标是进一步探索空间流分离的大脑皮层相关因素，并揭示其细胞机制。虽然猫一直被认为是空间听力研究的实验模型，但它们在活体细胞内和药理学实验中是不现实的。相反，像老鼠这样的小型啮齿动物非常适合进行这类研究。因此，我们选择了老鼠而不是猫作为拟议研究的模型。为了达到阐明空间流分离的细胞机制的目的，我们提出了三个具体的目标：1)评估大鼠初级听觉皮质(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。目标1将利用细胞外技术评估大鼠A1单位对来自自由场扬声器位置的噪声爆发刺激的空间敏感性，该刺激在方位上变化360度。目标2将实施空间流分离范式，该范式改编自我们实验室之前进行的一项心理物理研究。皮质反应将用细胞外技术记录下来，并用创新的方法和计算模型进行分析。目的3将结合细胞外记录和GABAA受体的药物阻断来确定皮质内抑制在空间流分离中的作用。这项建议将首次研究GABAA受体的皮质内抑制效应是否与A1中的空间流分离有关。我们对可能参与听觉流形成的潜在皮质内机制的研究将促进我们对A1中听觉场景分析如何完成的理解。具体地说，哪些特征是在皮质中从头合成的，通过皮质处理增强的，还是被动地从皮质下输入遗传来的？阐明空间流分离的各个方面的机制对于帮助助听器和人工耳蜗使用者设计在复杂听觉场景中增强听力的声音处理方案具有广泛的意义。

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.