Cortical Mechanisms Supporting Auditory Perceptual Learning

项目总结/摘要 候选人：候选人的长期目标是建立一个独立的研究计划，重点是 听觉系统长期知觉可塑性的神经机制。她以前的训练 为她提供了听觉生理学，感觉可塑性和行为神经科学的坚实基础。 在这里，她建议通过额外的清醒行为生理学培训来扩展自己的技能， 相关病毒（AAV）介导的细胞类型特异性视蛋白表达，以及无线光遗传学操纵。 清醒动物的神经活动。在K99阶段，她将准备过渡到 通过参加粉笔讲座、教学实践、工作面试、谈判和实验室等研讨会实现独立性 管理在指导阶段结束时，候选人将具备学术和实践技能 需要过渡到建立自己的实验室。在R 00期结束时，她 将有出版记录和初步数据需要产生一个高度竞争的R 01应用。 环境：K99阶段的培训将在纽约大学（NYU）神经科学中心进行， 一个优秀的环境，博士后水平的培训，在系统级神经科学。丹·萨尼斯博士， 该应用程序的主要导师，有一个既定的听觉神经科学研究计划，使用 一系列的方法，包括体外切片生理学，体内清醒行为生理学，钙成像， 心理物理学，以及最近的光遗传学。与位于纽约大学的Gordon Fishell博士合作， 医学院，提供了与AAV载体的Sanes实验室，允许有针对性的，细胞类型特异性 视蛋白表达Fishell博士提供了一封支持信，表示他愿意继续这项工作。 合作，无论是与博士Sanes在K99阶段的这个奖项，并与候选人直接，一旦 她获得了独立。其他指导将由丹尼尔波利博士（哈佛）和博士。 乔纳森弗里茨（马里兰州大学），在听觉神经科学界的领导人。 研究：声音检测的长期改进（一个被称为感知学习的过程）对于 语言习得和音乐训练。尽管它很重要，我们对神经机制的理解 潜在的感知学习仍然有限。此外，有证据表明，自上而下的调节， 与主动听力相关的皮层活动参与知觉学习，但尚不清楚是否存在一种 这些过程之间存在因果关系。拟议的研究将解决这些问题。 当动物接受声音探测训练时， 任务，揭示了动物学习时神经和行为改善之间的时间关系（K99）。 来自额叶皮层（R 00）的类似记录将建立知觉过程中自上而下活动的动态。 训练听觉皮层（K99）和额叶皮层内局部抑制回路的无线光遗传学激活 皮层（R 00）的研究将揭示这些大脑区域在感知学习中的因果作用。

PROJECT SUMMARY/ABSTRACT Candidate: The candidate's long-term goal is to establish an independent research program focusing on the neural mechanisms of long-term perceptual plasticity in the auditory system. Her previous training has provided her with a strong foundation in auditory physiology, sensory plasticity, and behavioral neuroscience. Here, she proposes to expand her skill set with additional training in awake-behaving physiology, adeno- associated virus (AAV)-mediated, cell-type specific opsin expression, and wireless optogenetic manipulation of neural activity in awake-behaving animals. During the K99 phase, she will prepare for the transition to independence by attending workshops on chalk talks, teaching practices, job interviews, negotiation, and lab management. By the end of the mentored phase, the candidate will have the academic and practical skills needed to transition to establish her own laboratory. By the completion of the R00 period of this award, she will have the publication record and preliminary data needed to generate a highly competitive R01 application. Environment: K99 phase training will take place at New York University's (NYU) Center for Neural Science, an outstanding environment for postdoctoral level training in systems-level neuroscience. Dr. Dan Sanes, the primary mentor for this application, has an established auditory neuroscience research program that uses a range of approaches, including in vitro slice physiology, in vivo awake-behaving physiology, calcium imaging, psychophysics, and more recently, optogenetics. A collaboration with Dr. Gordon Fishell, located at NYU's School of Medicine, has provided the Sanes Lab with AAV vectors, allowing for targeted, cell-type specific opsin expression. Dr. Fishell has provided a letter of support, indicating his willingness to continue this collaboration, both with Dr. Sanes during the K99 phase of this award, and with the candidate directly, once she achieves independence. Additional mentoring will be provided by Dr. Daniel Polley (Harvard), and Dr. Jonathan Fritz (University of Maryland), both leaders in the auditory neuroscience community. Research: Long-term improvement in sound detection, a process known as perceptual learning, is critical to language acquisition and musical training. Despite its importance, our understanding of the neural mechanisms underlying perceptual learning remains limited. Furthermore, evidence suggests that top-down modulations of cortical activity related to active listening are involved in perceptual learning, but it is unknown whether a causal relationship exists between these processes. The proposed research will address these issues. Wireless recordings will be made from the auditory cortex of animals as they are trained on a sound detection task, revealing the temporal relationship between neural and behavioral improvement as animals learn (K99). Similar recordings from frontal cortex (R00) will establish the dynamics of top-down activity during perceptual training. Wireless optogenetic activation of local inhibitory circuits within auditory cortex (K99) and frontal cortex (R00) will reveal the causal roles of these brain regions in perceptual learning.