Learning-dependent plasticity and mnemonic encoding in parieto-frontal networks

描述(由申请人提供)：我们有非凡的能力来学习和识别我们环境中对象和事件的行为意义或类别成员资格。破坏这种能力的疾病，如中风、阿尔茨海默病和精神分裂症，可能会导致受影响患者的日常功能出现严重问题。虽然对刺激和事件进行分类的能力对我们与世界互动的能力至关重要，但人们对如何进行分类知之甚少 这些类别是通过学习获得的。此外，关于类别和其他抽象现象是如何存储在内存中的，还有很多有待理解的地方。机械地理解我们如何学习刺激的行为相关性，以及这些信息是如何加载到记忆中的，可以极大地提高我们治疗影响认知功能的疾病的能力。先前的工作表明，在长期训练后，两个相互关联的皮质区域--外侧顶内(LIP)区和外侧前额叶(LPFC)--的神经元活动显示出对刺激类别成员的强烈而健壮的编码。然而，关于神经元类别表征是如何在学习过程中发展的，以及储存在长期记忆中的类别表征如何在行为过程中转移到短期记忆中，人们知之甚少。本项目的目标是阐明LIP和LPFC中类别学习的行为和神经元动力学，并了解任务复杂性如何影响短期记忆中的信息表征。首先，我们将记录在类别学习过程中的LIP和LPFC神经元群体，以了解神经元类别表征是如何作为学习的函数发展的。其次，我们将通过比较受试者在同一组运动刺激下的视觉分类和识别任务中的神经元活动，来检验LIP和LPFC中记忆神经元表征的任务依赖性。这些研究的结果将对大脑如何学习关于视觉刺激的抽象信息并将其保持在记忆中产生机械性的理解。拟议研究的长期目标是为了解和未来治疗影响学习、记忆和认知的疾病和状况提供基础。除了中风和阿尔茨海默病等神经疾病外，研究注意力缺陷障碍和阅读障碍等影响学习的疾病可能会受益于对学习和记忆背后的大脑机制的更详细了解。因此，从学习和记忆的神经基础研究中获得的知识可能会为治疗神经和认知障碍的下一代有价值的治疗方法提供帮助。 与公共健康相关：这项研究旨在更详细地了解认知概念，如关于类别的认知概念是如何学习和存储在记忆中的。理解这些想法的能力可能会被一系列神经和认知障碍所破坏，包括阿尔茨海默病、中风、注意力缺陷障碍、阅读障碍等。对学习和记忆背后的大脑过程进行更机械的了解，可能会为此类疾病的治疗提供有价值的基础，最终改善受认知能力障碍影响的人的生活和日常功能。

DESCRIPTION (provided by applicant): We have a remarkable ability to learn and recognize the behavioral significance, or category membership, of objects and events in our environment. Diseases that disrupt this ability, such as Stroke, Alzheimer's disease, and Schizophrenia, can cause serious problems in the daily function of affected patients. While the ability to categorize stimuli and events is critical to our ability to interact with the world, little is known about how these categories are learned. Furthermore, much remains to be understood about how categories and other abstract phenomena are stored in memory. A mechanistic understanding of how we learn the behavioral relevance of stimuli and how such information is loaded into memory could greatly enhance our ability to treat diseases that affect cognitive function. Prior work has revealed that neuronal activity in two interconnected cortical areas, the lateral intraparietal (LIP) area and lateral prefrontal cortex (LPFC), show strong and robust encoding of the category membership of stimuli following long-term training. However, relatively little is known about how neuronal category representations develop during the learning process itself, and how category- representations stored in long-term memory are transferred to short-term memory during behavior. The goals of this project are to elucidate the behavioral and neuronal dynamics of category learning in LIP and LPFC, and to understand how task complexity affects representation of information in short-term memory. First, we will record from populations of LIP and LPFC neurons during the category-learning process in order to understand how neuronal category representations develop as a function of learning. Second, we will examine the task-dependence of mnemonic neuronal representations in LIP and LPFC by comparing neuronal activity in subjects during visual categorization and identification tasks with the same set of motion stimuli. The results of these studies will yield a mechanistic understanding of how the brain learns abstract information about visual stimuli and maintains it in memory. The long term goal of the proposed studies is to provide a basis for the understanding and future treatments of the diseases and conditions which affect learning, memory, and recognition. In addition to neurological disorders such as Stroke and Alzheimer's disease, work on conditions that affect learning such as Attention Deficit Disorder and Dyslexia could benefit from a more detailed understanding of the brain mechanisms underlying learning and memory. Thus, the knowledge gained from studying the neural basis of learning and memory will likely shed light onto valuable next-generation treatments for neurological and cognitive disorders. PUBLIC HEALTH RELEVANCE: This research aims to achieve a more detailed understanding of how cognitive ideas, such as those about categories, are learned and stored in memory. The ability to understand such ideas can be disrupted by a wide range of neurological and cognitive disorders, including Alzheimer's disease, Stroke, Attention Deficit Disorder, Dyslexia, and more. A more mechanistic understanding of the brain processes underlying learning and memory will likely provide a valuable basis for the treatment of such diseases, ultimately improving the lives and daily function of the people affected by disorders involving cognitive faculties.