Cortical Mechanisms Supporting Auditory Perceptual Learning

项目摘要/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，专注于 听觉系统中长期知觉可塑性的神经机制。她之前的训练已经 为她提供了在听觉生理学、感觉可塑性和行为神经科学方面的坚实基础。 在这里，她建议通过额外的清醒行为生理学、腺病-- 相关病毒(AAV)介导的细胞类型特异性视蛋白表达和无线光遗传操作 清醒行为动物的神经活动。在K99阶段，她将准备过渡到 通过参加关于粉笔演讲、教学实践、工作面试、谈判和实验室的研讨会来独立 管理层。在指导阶段结束时，应聘者将拥有学术和实践技能 她需要过渡到建立自己的实验室。在本奖项的R00期结束时，她 将拥有生成极具竞争力的R01应用程序所需的发布记录和初步数据。 环境：K99阶段培训将在纽约大学(NYU)神经科学中心进行， 在系统级神经科学方面进行博士后级别培训的出色环境。丹·萨内斯博士， 这个应用程序的主要导师，已经建立了一个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，活体清醒生理学，钙成像， 心理物理学，以及最近的光遗传学。与纽约大学的戈登·菲舍尔博士合作 医学院，为Sanes实验室提供了AAV载体，允许有针对性的、细胞类型特定的 视蛋白表达。菲舍尔博士已经提供了一封支持信，表明他愿意继续这样做 在该奖项的K99阶段与Sanes博士合作，以及与候选人直接合作，一次 她实现了独立。丹尼尔·波利博士(哈佛大学)和丹尼尔·波利博士将提供额外的指导。 乔纳森·弗里茨(马里兰大学)，两人都是听神经科学界的领导者。 研究：声音检测的长期改进，一种称为知觉学习的过程，对 语言习得和音乐训练。尽管它很重要，但我们对神经机制的理解 潜在的知觉学习仍然有限。此外，有证据表明，自上而下的调节 与主动倾听相关的大脑皮层活动与知觉学习有关，但尚不清楚 这些过程之间存在因果关系。拟议的研究将解决这些问题。 无线录音将从动物的听觉皮质进行，因为它们接受了声音检测的训练 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)。 来自额叶皮质(R00)的类似记录将建立知觉过程中自上而下活动的动力学 训练。听皮层(K99)和额叶内局部抑制回路的无线光遗传激活 大脑皮层(R00)将揭示这些大脑区域在知觉学习中的因果作用。

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.