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: 8878211
• 负责人: Justin Daniel Yao
• 金额: $ 2.52万
• 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 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8878211
• 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; Health; 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; neural correlate; neuromechanism; 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，听众面临多个交错的声音序列，必须以某种方式将其分配给相应的声源。此过程称为“流隔离”，其中每个“流”代表来自特定源的声音序列的感知相关性。声源的空间分离有助于识别多个声音序列（即多个“流”），属于不同的来源。听觉神经科学中的一个核心问题是听觉流在大脑中的形成方式。该提案的目的是进一步探索空间流分离的皮质相关性，并发现它们的细胞机制。尽管猫作为空间听力研究的实验模型受到青睐，但它们对于体内细胞内和药理学实验是不切实际的。取而代之的是，像大鼠这样的小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。为了实现阐明空间流分离的细胞机制的目标，我们提出了三个特定的目的：1）评估大鼠一级听觉皮层的空间灵敏度（A1）； 2）表征大鼠A1中的空间流分离； 3）确定大鼠A1中空间流分离的神经机制。 AIM 1将利用细胞外技术来评估大鼠A1单位对噪声爆发刺激的空间敏感性，这些噪声爆发刺激来自自由场扬声器的位置，这些位置在方位角变化了360度。 AIM 2将实施由以前在我们实验室中进行的心理物理研究改编的空间隔离范式。皮质反应将使用细胞外技术记录，并使用创新的方法和计算模型进行分析。 AIM 3将将细胞外记录与GABAA受体的药理阻滞结合，以确定皮质内抑制在空间流隔离中的作用。该提议首次研究GABAA受体的皮质内抑制作用是否解释了A1中的空间流分离。我们对可能参与听觉流的形成的潜在皮质内机制的检查将提高我们对A1中听觉场景分析的理解。具体而言，在皮质中合成了哪些特征，通过皮质加工增强或从皮质下输入被动遗传？阐明负责空间流隔离各个方面的机制在协助助听器和人工耳蜗植入物用户的复杂听觉场景中增强听力的声音处理方案的设计具有广泛的含义。