Investigating neural substrates of generalization from past experience

项目总结/摘要： 在新的环境中，我们有一种非凡的能力，可以从先前的学习中归纳出来，帮助我们实现目标。这 能力被认为取决于我们表现相关经验中存在的共同关系的能力， 例如在各种超市中的任何一个超市进行食品杂货购物所涉及的一系列步骤。这些背景- 任务的一般化表示被称为模式。在大脑中，图式被认为是 由神经集合来表示，这些神经集合在不同的上下文中对任务进行类似的编码。最近的研究发现， 前额叶皮层（PFC）的图式表征。这些模式表示如何形成和支持 然而，人们对新环境下的快速学习还没有很好的理解。 长期记忆形成的一个公认的理论，即系统巩固理论，提供了一个 图式表征如何在大脑中产生的模型。根据这一理论，海马体（HPc） 在新的环境中快速编码特定事件的记忆。在接下来的休息时间里，这些HPc 记忆被重新激活，这被认为会导致相应记忆的长期增强 在大脑皮层内部和各处都有痕迹由此产生的新皮层记忆被认为是强调共同的 跨上下文中的功能，为模式表示提供基础。我们的总体假设是基于 系统巩固理论认为，HPc记忆激活促进图式的形成 PFC中的表示（目标1和3），以及在新的上下文中表达这些表示，反过来又使 快速学习（目标2和3）。为了验证这一假设，我们将在新的环境中配对大鼠学习模型， 大鼠表现出快速的学习给予先前的经验，同时记录PFC和HPc神经 总体研究（目标1-3）和因果干预研究（目标3）。 这些目标的完成有可能对神经基质产生根本性的见解 从过去的经验中总结出来的。我们的研究结果还将为支持或反对 系统整合理论的长期预测，到目前为止，在缺乏 分发同步录音。这项研究将在我的研究赞助商洛伦博士的实验室进行 弗兰克，在加州大学，旧金山弗朗西斯科（UCSF）。弗兰克实验室位于桑德勒神经科学 中心，这是一个高度创新和协作社区的教师和学生追求 神经科学问题我在这个奖学金下的培训计划将为我作为一个独立的职业生涯做好准备。 他是一位学术医生科学家，长期目标是揭示认知背后的神经计算。 流程.除了拟议的研究外，这一准备将通过严格的定量 课程作业，有计划地参与充满活力的知识社区，以及临床活动。

PROJECT SUMMARY/ABSTRACT: In new settings, we have a remarkable ability to generalize from prior learning to help us achieve our goals. This capacity is thought to depend on our ability to represent the common relationships present in related experiences, such as the series of steps involved in grocery shopping at any one of a variety of supermarkets. These context- generalized representations of a task have been termed schemas. In the brain, schemas are thought to be represented by neural ensembles that encode a task similarly across contexts. Recent work has identified schema representations in the prefrontal cortex (PFC). How these schema representations form and support rapid learning in new contexts, however, is not well understood. A well-established theory of long-term memory formation known as systems consolidation theory provides a model for how schema representations may arise in the brain. According to this theory, the hippocampus (HPc) rapidly encodes memories of specific episodes in new contexts. In periods of rest that follow, these HPc memories are reactivated, and this is thought to result in the long-lasting strengthening of corresponding memory traces within and across neocortex. The resulting neocortical memories are thought to emphasize common features across contexts, providing a basis for schema representation. Our overarching hypothesis based on the theory of systems consolidation is that HPc memory reactivation promotes the formation of schema representations in PFC (Aims 1 and 3), and expression of these representations in new contexts in turn enables rapid learning (Aims 2 and 3). To test this hypothesis, we will pair a rat model of learning in new contexts wherein rats exhibit rapid learning given prior experience, with simultaneous recordings of PFC and HPc neural ensembles (Aims 1–3) and causal intervention studies (Aim 3). Completion of these Aims has the potential to yield fundamental insights into the neural substrates of generalization from past experience. Our findings will additionally provide important evidence for or against longstanding predictions of systems consolidation theory that have so far been difficult to test in the absence of distributed simultaneous recordings. This study will be carried out in the lab of my research sponsor, Dr. Loren Frank, at the University of California, San Francisco (UCSF). The Frank lab is located in Sandler Neurosciences Center, which is home to a highly innovative and collaborative community of faculty and students pursuing neuroscience questions. My training plan under this fellowship will prepare me for an independent career as an academic physician scientist with the long-term goal of revealing neural computations underlying cognitive processes. In addition to the proposed research, this preparation will be achieved through rigorous quantitative coursework, planned engagement with vibrant intellectual communities, and clinically geared activities.