NCS-FO: Unraveling Cortical Circuits for Auditory Scene Analysis

在日常社交场合中，听力正常的人类能够在其他人说话和其他声源的同时听到说话者的声音。这是一个名为听觉场景分析的一般问题的例子。经过50多年的研究，听觉场景分析的理解在神经科学、计算机科学、语音识别和工程等多个领域仍然是一个具有挑战性的问题。虽然对于机器和听力受损的听众来说，这是一个困难的问题，但听力正常的人类相对容易地解决了这个问题。这表明大脑中存在这个问题的解决方案，但这个解决方案仍然未知。这个项目将研究大脑是如何解决这个问题的。通过揭示大脑中有助于解决问题的电路，该项目将最终通过在医疗设备中的应用来提高生活质量，例如助听器和人工耳蜗；通过技术方面的应用来造福社会，例如语音识别应用；并创建一个教育平台，培训学生整合不同学科的知识来解决具有挑战性和重要的社会问题。不同声源的空间位置是听觉场景分析的重要组成部分。听觉皮层以其独特的空间声音处理能力，被认为在听觉场景分析中发挥着重要作用，尽管其潜在的神经网络机制在很大程度上仍不清楚。这个项目将研究小鼠初级听觉皮质中用于听觉场景分析的皮质回路，使用强大的光遗传学工具来研究自下而上和自上而下的机制。首先，研究人员将研究行为状态对不同大脑皮层声音混合物的大脑皮层空间表征的影响，并测试这样的空间表征在大脑皮层和动物的行为状态之间存在差异的假设。其次，研究人员将利用光遗传学操作，研究初级听觉皮质中小白蛋白阳性(PV)抑制中间神经元与生长抑素阳性(SOM)抑制中间神经元之间的因果关系，并检验PV中间神经元在调节自下而上信号方面的关键作用，而SOM中间神经元在活跃的行为状态下选择性地参与。最后，研究人员将构建包括兴奋性、PV和SOM神经元在内的初级听觉皮质的计算模型，以解释实验结果并对未来的实验做出预测。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

In everyday social situations, normal hearing humans are able to listen to a speaker in the midst of other people talking and other sound sources. This is an example of a general problem termed auditory scene analysis. The understanding of auditory scene analysis remains a challenging problem in a diverse range of fields such as neuroscience, computer science, speech recognition and engineering, after more than 50 years of research. Although a difficult problem for machines and hearing impaired listeners, humans with normal hearing solve it with relative ease. This suggests the existence of a solution to this problem in the brain, but this solution remains unknown. This project will investigate how the brain solves this problem. By revealing circuits in the brain that contribute to the solution, this project will ultimately improve quality of life through applications in medical devices, e.g., hearing aids and cochlear implants; benefit society through applications in technology, e.g., applications for speech recognition; and create an educational platform to train students to integrate knowledge from a variety of disciplines to address challenging and important societal problems.The spatial location of different sound sources is an important component of auditory scene analysis. The auditory cortex, with its unique spatial sound processing ability, is thought to play an important role in auditory scene analysis, although the underlying neural network mechanisms remain largely unknown. This project will investigate cortical circuits for auditory scene analysis in the primary auditory cortex of the mouse, employing powerful optogenetic tools to investigate both bottom-up and top-down mechanisms. First, the investigators will examine the influence of behavioral states on cortical spatial representations of sound mixtures across different cortical layers and test the hypotheses that such spatial representations vary across cortical layers and behavioral states of the animal. Second, the investigators will examine the causal role of parvalbumin positive (PV) inhibitory interneurons versus somatostatin positive (SOM) inhibitory interneurons in the primary auditory cortex, using optogenetic manipulations, and test the hypothesis that PV interneurons are critical in mediating bottom-up signaling, whereas SOM interneurons are selectively engaged during active behavioral states. Finally, the investigators will construct a computational model of the primary auditory cortex including excitatory, PV and SOM neurons to explain the experimental results and make predictions for future experiments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.