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

描述（由申请人提供）：在一个复杂的听觉场景中，听众面临着多个交错的声音序列，这些声音序列必须以某种方式被分配到相应的声源。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感知关联。声源的空间分离有助于识别属于不同声源的多个声音序列（即多个“流”）。听觉神经科学的一个核心问题是听觉流是如何在大脑中形成的。本研究的目标是进一步探索空间流分离的皮层相关因素，并揭示其细胞机制。虽然猫被认为是空间听力研究的实验模型，但它们在体内细胞内和药理实验中是不切实际的。相反，像老鼠这样的小型啮齿动物更适合这类研究。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)评估大鼠初级听觉皮层（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单元对来自360度方位变化的自由场扬声器位置的噪声突发刺激的空间敏感性。目标2将实现空间流分离范式，该范式改编自我们实验室先前进行的心理物理学研究。皮质反应将记录与细胞外技术和分析创新的方法和计算模型。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。本研究将首次探讨GABAA受体的皮质内抑制作用是否导致了A1的空间流分离。我们对可能参与听觉流形成的潜在皮层内机制的研究将促进我们对听觉场景分析如何在A1中完成的理解。具体来说，哪些特征是在皮层中重新合成的，通过皮层处理增强的，还是从皮层下输入被动继承的？阐明导致空间流分离的各个方面的机制，对于帮助设计声音处理方案以增强助听器和人工耳蜗使用者在复杂听觉场景中的听力具有广泛的意义。

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.