Neural plasticity underlying memory formation for vocalizations sequentially learned during a sensitive period in development

摘要 在理解神经活动以及解剖学和生理学的偏侧化方面存在着根本的差距 神经可塑性影响语言习得。习得第二语言所必需的可塑性(L2) 人们对童年后期的了解就更少了。因此，确定L2中延迟的原因是一项具有挑战性的工作 在神经层面进行学习。获得一只鸣鸟的歌声与人类的语音学习是平行的 行为和神经水平，从而提供了研究神经的独特机会 学习和记忆的机制。长期目标是确定细胞和系统级别 鸟类获取、存储和恢复听觉记忆的机制。父母的目标 获奖的目的是确定与声音可塑性有关的神经系统，这些神经系统与模仿第二个元素有关 宋代模型(S2)正在开发中。根据初步数据提出的中心假设是 这种偏侧化的神经可塑性是成功获得多个听觉记忆所必需的。这 正在通过追求两个具体目标来检验假说：1)定义与以下因素有关的大脑活动的侧化 感觉运动学习中的发声可塑性；2)决定生理可塑性对发声的影响 学习。在第一个目标中，早期听觉环境的操作将与分析 歌唱学习和量化血液氧合水平依赖(BOLD)反应。强壮 初步数据提供了证据，斑马雀可以从两个不同的发声模式中学习元素 开发中的时间点，以及试点功能磁共振研究表明，在 申请人的实验室。在第二个目标中，用免疫组织化学对抑制细胞类型进行分类 在发展的关键时刻使用；从两个不同的声乐模型学习歌曲将被量化 并将确定对发声可塑性做出贡献的抑制细胞类型。方法是 创新，通过结合纵向功能成像和三重标记方法，它正在克服 研究L2学习中神经可塑性的基本过程的内在局限性 通过使用已建立的动物模型来研究人类。这项研究意义重大，因为通过使用不同的方法 在人类中可用，我们将获得对形成的可塑性的机械理解 声乐学习者的多重听觉记忆。这将提供对自适应感觉运动的理解 在生物体的一生中，整合有助于发声行为。这样做的理由是 补充说，由于与COVID相关的封锁的影响，我们的繁殖群体正在经历 缺乏歌曲的多样性。这导致了实验上的挑战，因为歌曲多样性对 家长奖的目标2中提出的实验。补充活动的重点是开发一种 从遗传和文化上多样化地供应这种不同寻常的模式生物，以完成拟议的 家长奖中的活动。

Summary There is a fundamental gap in understanding how lateralized neural activity, and anatomical- and physiological neural plasticity affect language acquisition. The plasticity that is necessary to acquire a second language (L2) later in childhood is even less well understood. Thus, it is challenging to identify the cause of delays in L2 learning at the neural level. The acquisition of a songbird’s song parallels human speech learning at the behavioral as well as the neural level and thus provides unique opportunities to investigate the neural mechanisms of learning and memory. The long-term goal is to determine the cellular and system-level mechanisms through which birds acquire, store, and retrieve auditory memories. The objective of the parent award is to determine the neural systems involved in vocal plasticity related to imitating elements from a second song model (S2) later in development. The central hypothesis, formulated on the basis of preliminary data, is that lateralized neural plasticity is necessary for successful acquisition of multiple auditory memories. This hypothesis is being tested by pursuing two specific aims: 1) Define lateralization of brain activity in relation to vocal plasticity during sensorimotor learning; and 2) Determine the impact of physiological plasticity on vocal learning. In the first aim, manipulations of the early auditory environment will be combined with analysis of song learning and quantification of the Blood Oxygenation Level Dependent (BOLD) response. Strong preliminary data provide evidence that zebra finches can learn elements from different vocal models at two time points in development, and pilot fMRI studies indicate feasibility to perform the proposed studies in the applicant’s laboratory. In the second aim, classification of inhibitory cell types with immunohistochemistry will be used at critical moments in development; song learning from two different vocal models will be quantified and the inhibitory cell types that are contributing to vocal plasticity will be determined. The approach is innovative, as by combining longitudinal functional imaging and triple labeling methods, it is overcoming inherent limitations to studying the fundamental processes underlying neural plasticity for L2 learning in humans by using an established animal model. The research is significant, because by using approaches not available in humans, we will gain a mechanistic understanding of the plasticity that underlies formation of multiple auditory memories in vocal learners. This will provide an understanding of adaptive sensorimotor integration contributing to vocal behavior throughout an organism’s lifetime. The justification for this supplement is that due to the impact of the COVID related lock-down, our breeding colony is experiencing a lack of song diversity. This has resulted in experimental challenges as song diversity is critical to the experiments proposed in Aim 2 of the parent award. Supplement activities are focused on developing a genetically and culturally diverse supply of this unusual model organism in order to complete the proposed activities in the parent award.