Distributed Representation of Working Memory in Prefrontal Cortex

前额皮质工作记忆的分布式表示

• 批准号: 7806855
• 负责人: Ronald James Cotton
• 金额: $ 3.47万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-11-15 至 2013-11-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806855
• 关键词: Accounting; Address; Adverse effects; Attention deficit hyperactivity disorder; Brain region; Cells; Chronic; Cognitive; Complex; Comprehension; Cues; Decision Making; Disease; Environment; Fire - disasters; Functional disorder; Gossypium; Image; Implant; Language; Lead; Maintenance; Maps; Memory; Methods; Monkeys; Neurons; Pattern; Pharmacology; Play; Population; Prefrontal Cortex; Recurrence; Research; Resolution; Role; Schizophrenia; Series; Short-Term Memory; Stimulus; Structure; Techniques; Testing; Time; Work; base; design; human disease; improved; in vivo; insight; member; theories; two-photon

DESCRIPTION (provided by applicant): Working memory is the ability to retain and manipulate information when it is no longer present in the environment, and is a fundamental requirement for numerous cognitive abilities like decision-making and language comprehension. The prefrontal cortex plays a critical role in working memory, and it has been shown that neurons fire selectively to cues that must be remembered when they are removed, providing evidence that working memory may be "held" in this region of the brain. Recent work has shown that the firing patterns of neurons during the delay period shows complex dynamics that are not accounted for by many classical theories of prefrontal cortex function. I conjecture that working memory is maintained by small, spatially clustered, sub-populations of cells that activate temporarily before activating another sub- population, like a series of dominos, where the sequence reflects what is remembered and the domino symbolizes the sub-population. This conjecture is based upon recent studies and my preliminary results showing that the majority of neurons represent the memory only transiently and that pairs of neurons seem to interact briefly during a trial. I propose two specific aims designed to test this conjecture and provide information towards a more mechanistic understanding of how prefrontal-cortical circuits maintain activity during working memory tasks. The first specific aim is to test the hypothesis that working memory is represented by a sequence of discrete states, where a state is associated with a small neuronal subpopulation that activates transiently during the delay period, and that different memoranda evoke different sequences of states, their preferred stimulus. The second specific aim is to test the hypothesis that similarly tuned neurons in prefrontal cortex or neurons associated with a state show spatial clustering. These specific aims will be addressed through a combination of chronically implanted arrays of tetrodes and in vivo two-photon imaging while monkeys are engaged in a working memory task. These studies will provide a mechanistic insight into who working memory contents are represented and maintained across a population of neurons. This is important because dysfunctions of working memory are associated with schizophrenia and attention-deficit/hyperactivity disorder. By better understanding working memory maintenance, it may open the door for more targeted pharmacology with improved side-effect profiles.

描述(申请人提供)：工作记忆是当信息不再存在于环境中时保留和处理信息的能力，是许多认知能力的基本要求，如决策和语言理解。前额叶皮质在工作记忆中起着关键作用，已有研究表明，神经元有选择地对被移除时必须记住的线索进行放电，这为工作记忆可能在大脑的这一区域“持有”提供了证据。最近的研究表明，神经元在延迟期的放电模式表现出复杂的动力学，这是许多经典的前额叶皮质功能理论无法解释的。我推测，工作记忆是由空间上聚集的小细胞亚群维持的，这些细胞在激活另一个亚群之前暂时激活，就像一系列多米诺骨牌一样，其中序列反映了记忆的内容，多米诺骨牌象征着亚群。这一猜测是基于最近的研究和我的初步结果，结果表明，大多数神经元只代表短暂的记忆，而且成对的神经元似乎在试验期间短暂地相互作用。我提出了两个特定的目标，旨在检验这一猜测，并为更机械地理解前额叶皮层回路如何在工作记忆任务中维持活动提供信息。第一个具体目标是检验这样一个假设，即工作记忆是由一系列离散的状态代表的，其中一个状态与一个在延迟期短暂激活的小神经元亚群相关，并且不同的记忆会引起不同的状态序列，这是它们首选的刺激。第二个特定的目的是检验这样一个假设，即前额叶皮质中类似调谐的神经元或与某一状态相关的神经元表现出空间聚集。这些特定的目标将通过长期植入的四极管阵列和体内双光子成像相结合来实现，而猴子正在进行工作记忆任务。这些研究将提供一种机械性的洞察，了解在一群神经元中谁代表和维持谁的工作记忆内容。这一点很重要，因为工作记忆功能障碍与精神分裂症和注意力缺陷/多动障碍有关。通过更好地了解工作记忆的维持，它可能会为更有针对性的药理学打开大门，改善副作用。