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

在理解如何将神经活动和解剖学-以及 生理神经可塑性影响语言习得。获得第二个孩子所必需的可塑性 童年后期的语言(L2)就更不能被理解了。因此，找出 在神经层面上的二语学习延迟。获得一只鸣鸟的歌声与人类的言语相似 在行为和神经层面上的学习，因此提供了独特的机会来研究 学习和记忆的神经机制。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。该计划的目标是 建议的更新应用是确定与发声可塑性相关的神经系统 模仿后来开发的第二首歌曲模型(S2)中的元素。中心假说，公式化 根据初步数据，偏侧化的神经可塑性是成功获得 多个听觉记忆。这一假设将通过追求两个具体目标来检验，这将：1)定义 感觉运动学习中大脑活动与发声可塑性的偏侧化；以及2)决定 生理可塑性对声乐学习的影响。在第一个目标中，早期听觉的操纵 将环境与歌曲学习分析和血氧含量量化相结合 级别相关(粗体)响应。强劲的初步数据提供了斑马雀可以学习的证据 来自不同发声模型的元素在发育的两个时间点，以及试点功能磁共振研究表明 在申请人的实验室进行拟议研究的可行性。在第二个目标中，分类 免疫组织化学的抑制性细胞类型将用于发育的关键时刻 从两个不同的发声模型中学习将被量化，以及对 声带可塑性将被确定。这些方法中的每一种，包括使用商业上可用的 抗体和免费提供的歌曲和图像分析软件，此前已在 鸣禽，结合试点研究的数据，提供了证据证明了 在私家侦探的实验室里进行的研究。这种方法是创新的，因为它结合了纵向功能成像 和三重标记法，它克服了研究基本过程的固有局限性 利用已建立的动物模型研究人类第二语言学习的神经可塑性。建议数 研究意义重大，因为通过使用人类无法获得的方法，我们将获得一种机械性的 理解声乐学习者多重听觉记忆形成的可塑性。这 将有助于理解自适应感觉运动整合在整个发声行为中的作用 一个有机体的一生。

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 proposed renewal application 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 will be tested by pursuing two specific aims, which will: 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. Each of these methods, including the use of commercially available antibodies and freely available song and image analysis software, has previously been established in songbirds, which, in combination with data from pilot studies, provides evidence for the feasibility of the proposed studies in the PI's lab. 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 proposed 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.