Non-sensory Circuits for Auditory Perceptual Learning

项目摘要 训练可以使我们的感知技能更加敏锐和精细。在听觉系统中，这个过程被称为 感知学习-塑造母语和非母语的习得，并可以提高 语音和音乐识别。以往的工作突出了重要的 非感觉过程（如注意力和奖励）对知觉学习的贡献，但 对潜在的神经回路机制仍然知之甚少。最近的证据表明， 眶额皮层（OFC），一个涉及奖励和期望信号的前额叶皮层区域，以及 对感觉皮层处理进行自上而下的控制。本项目将探讨竞争事务办公室的贡献 蒙古沙鼠是听觉研究的经典模式生物。我们 根据以前和正在进行的工作，总体假设是， 加强了从眶额皮层到听觉皮层的下行投射，导致逐渐改善， 听觉皮层的敏感性是感知学习的基础。我们提出了三个具体目标来测试这一点 假说.在目标1中，我们使用多通道电生理学和通路特异性纤维光度法， 确定听觉任务的训练是否加强了从OFC到听觉的下行投射， 增加突触前活动。在目标2中，我们将联合收割机药理学和光遗传学方法相结合， 确定OFC是否通过以下方式调节行为动物的听觉皮层处理和/或感知 一个下行的单突触投射，并揭示这种能力是否增强后，知觉 学习最后，在目标3中，我们确定听觉皮层投射神经元的光遗传激活是否 在OFC中足以改善行为动物的听觉皮层和感知灵敏度， 缺乏训练。总之，我们的实验联合收割机结合了一系列强有力的体内工具来解剖 支持听觉感知学习的神经回路机制。感知学习的重要性 改善听力受损的听众的听觉技能，并中断个人的感知学习 与神经发育障碍，如诵读困难和自闭症，突出了一个更完整的迫切需要， 描述了感知学习是如何在大脑中实现的。

PROJECT SUMMARY Training can sharpen and refine our perceptual skills. In the auditory system, this process— termed perceptual learning— shapes the acquisition of both native and non-native languages, and can improve speech and music recognition in users of assisted listening devices. Previous work has highlighted important contributions of non-sensory processes (such as attention and reward) to perceptual learning, but the underlying neural circuit mechanisms remain poorly understood. Recent evidence suggests the involvement of the orbitofrontal cortex (OFC), a prefrontal cortical region implicated in signaling reward and expectation, and in exerting top-down control of sensory cortical processing. This project will explore the contribution of the OFC to auditory perceptual learning in a classic model organism for auditory studies, the Mongolian gerbil. Our overarching hypothesis, informed by previous and ongoing work, is that training on an auditory task strengthens a descending projection from the OFC to the auditory cortex, leading to gradual improvements in auditory cortical sensitivity that underlie perceptual learning. We propose three specific aims to test this hypothesis. In Aim 1, we use multichannel electrophysiology and pathway-specific fiber photometry to determine whether training on an auditory task strengthens a descending projection from the OFC to auditory cortex by increasing presynaptic activity. In Aim 2, we combine pharmacological and optogenetic methods to determine whether the OFC modulates auditory cortical processing and/or perception in behaving animals via a descending monosynaptic projection, and reveal whether this capability is enhanced after perceptual learning. Finally, in Aim 3 we determine whether optogenetic activation of auditory cortical-projecting neurons in the OFC is sufficient for improving auditory cortical and perceptual sensitivity in behaving animals in the absence of training. In summary, our experiments combine a powerful array of in vivo tools to dissect the neural circuit mechanisms that support auditory perceptual learning. The importance of perceptual learning for improving auditory skills in hearing impaired listeners, and the disruption of perceptual learning in individuals with neurodevelopmental disorders, like dyslexia and autism, highlight an urgent need for a more complete description of how perceptual learning is implemented in the brain.