Prefrontal cortex and memory storage

前额皮质和记忆存储

• 批准号: 7104809
• 负责人: PRAMOD K DASH
• 金额: $ 31.56万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7104809
• 关键词: behavior test; behavioral /social science research tag; cAMP response element binding protein; cognition; conditioning; dopamine; dopamine receptor; fear; gene induction /repression; hippocampus; laboratory rat; long term memory; mitogen activated protein kinase; molecular psychobiology; neural plasticity; prefrontal lobe /cortex

DESCRIPTION (provided by applicant): The prefrontal cortex (PFC) plays a critical role for behaviors that require a high level of mental integration. Damage to this structure results in an inability to select, maintain, and associate temporally disconnected stimuli. Although these dysfunctions have been attributed to disruptions in prefrontal activity and an inability to learn, they also could, however, result from a deficit in prefrontal memory storage. Our preliminary data show that in addition to the hippocampus, the medial RFC is involved in long-term memory storage for trace fear conditioning, a hippocampal-dependent associative learning paradigm. Training-related activation of extracellular signal-regulated kinase (ERK) occurred in the mPFC prior to that observed in the hippocampus, suggesting that mPFC plasticity may not depend on hippocampal information storage (or plasticity). As dopamine has been repeatedly shown to be necessary for proper prefrontal function, dopamine D1 receptor activity may modulate mPFC memory storage. Based on these observations and others, the present proposal will test the general hypothesis that information is stored long-term within the prefrontal cortex as a direct result of training in higher cognitive tasks. The three Specific Aims are: (1) To examine if molecular correlates of long-term memory occur in the mPFC as a result of trace fear conditioning (2) To examine the contribution of mPFC dopamine receptors in long-term memory for trace fear conditioning. (3) To examine the interaction between hippocampal and mPFC plasticity during memory storage for trace fear conditioning. Presently, there is an incomplete understanding of the process of memory storage. Investigation of PFC memory storage could be crucial to our understanding of this process and to the contribution of memory storage within the mPFC in guiding complex behaviors. The study will explore the role of the prefrontal cortex in long-term memory storage. As the function of the prefrontal cortex is often compromised as a result of neurological and psychiatric disorders, in aging, and following brain injury, an understanding of the role of this structure in long-term memory will provide information that will help guide treatment strategies for these conditions.

描述（由申请人提供）：前额皮质（PFC）对于需要高水平心理整合的行为起着至关重要的作用。该结构的损坏导致无法选择、维持和关联暂时断开的刺激。尽管这些功能障碍被归因于前额叶活动中断和学习能力丧失，但它们也可能是由于前额叶记忆存储缺陷造成的。我们的初步数据表明，除了海马体之外，内侧 RFC 还参与微量恐惧调节的长期记忆存储，这是一种依赖于海马体的联想学习范式。训练相关的细胞外信号调节激酶 (ERK) 激活发生在 mPFC 中，早于在海马中观察到的激活，表明 mPFC 可塑性可能不依赖于海马信息存储（或可塑性）。由于多巴胺已被反复证明对于正常的前额叶功能是必需的，因此多巴胺 D1 受体活性可能会调节 mPFC 的记忆存储。基于这些观察和其他观察，本提案将检验以下一般假设：信息长期存储在前额皮质内，作为高级认知任务训练的直接结果。三个具体目标是： (1) 检查 mPFC 中是否因微量恐惧调节而出现长期记忆的分子相关性 (2) 检查 mPFC 多巴胺受体在长期记忆中对微量恐惧调节的贡献。 (3) 检查海马和 mPFC 可塑性在记忆存储过程中微量恐惧调节过程中的相互作用。目前，人们对记忆存储过程的理解还不完全。对 PFC 内存存储的研究对于我们理解这一过程以及 mPFC 内存存储在指导复杂行为方面的贡献至关重要。该研究将探讨前额叶皮层在长期记忆存储中的作用。由于前额皮质的功能经常因神经和精神疾病、衰老和脑损伤而受到损害，因此了解该结构在长期记忆中的作用将提供有助于指导治疗策略的信息。这些条件。