Phase sequences of posterior parietal cortex ensembles and sequence learning

描述(申请人提供)：学习顺序是我们日常生活的一部分，从穿衣服到记住一天中的事件顺序。人类和其他患有精神障碍的动物在许多类型的序列学习方面都有问题。这项拟议的研究的目的是了解大脑回路是如何学习和编码空间序列的，这样未来的实验就可以测量大脑对可能导致精神障碍的序列的编码缺陷。目前，正常大脑如何完成序列学习的动物模型还不存在，这对于理解是什么出了问题导致缺陷是必要的。我们的实验室在开发序列学习模型方面取得了进展，通过同时记录大脑中的许多神经元，而大鼠学习导航到围绕圆形竞技场排列的一系列空间位置。这项任务让我们开始了解大脑的一部分--海马体--如何编码动物在这个空间序列中的位置；然而，我们还不知道大脑如何将序列中的位置信息转化为运动反应，以导航到下一个奖励位置。以前的研究表明，顶叶皮质可能会为序列中的当前位置翻译适当的运动反应。因此，我将研究大脑将序列中的位置信息转化为适当的运动反应的机制。在三个不同的实验中，我将评估：a)在顶叶皮质编码空间线索时使用的参照系(以人为中心还是以世界为中心)；b)序列学习过程中顶叶皮质的活动模式；c)顶叶皮质对已学习序列编码的贡献(具体地说，当顶叶皮质在空间序列学习和记忆的特定部分受到抑制时会发生什么)。这些初步实验将为序列学习的神经基础提供基础，这样我们就可以评估大脑对可能导致精神障碍的序列编码的缺陷。

DESCRIPTION (provided by applicant): Learning sequences is part of our daily lives, from getting dressed to remembering the event sequence of our day. Humans and other animals who develop mental disorders both have problems with many types of sequence learning. The objective of the proposed research is to understand how spatial sequences are learned and encoded by brain circuits so future experiments can measure deficits in brain coding of sequences that may underlie mental disorders. Currently, an animal model of how the normal brain accomplishes sequence learning does not exist and is necessary for understanding what goes wrong to produce deficits. Our laboratory has made progress towards developing a model of sequence learning by recording simultaneously from many neurons in the brain while rats learn to navigate to a series of spatial locations arranged around a circular arena. This task has allowed us to begin to understand how part of the brain, the hippocampus, encodes where the animal is in this spatial sequence; however, we do not yet know how the brain translates this information about position in the sequence into a motor response to navigate to the next reward location. Previous research suggests that the parietal cortex may translate an appropriate motor response for the current position in the sequence. Therefore, I will investigate the brain mechanism for translating information about position in a sequence to an appropriate motor response. In three different experiments, I will assess: a) the frames of reference (person centered vs world centered) that are used when spatial cues are encoded in the parietal cortex; b) activity patterns in the parietal cortex during sequence learning; c) contributions of the parietal cortex to encoding learned sequences (specifically, what happens when the parietal cortex is inhibited during particular portions of spatial sequence learning and memory). These initial experiments will provide a foundation for the neural basis of sequence learning so that we can assess deficits in brain coding of sequences that may underlie psychiatric disorders.