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）：前额叶皮层（PFC）对于需要高度精神整合的行为起着至关重要的作用。对这种结构的损害导致无法选择，维护和关联暂时断开的刺激。尽管这些功能障碍归因于前额叶活动的中断和无法学习，但是它们也可能是由于前额叶存储器存储的赤字而导致的。我们的初步数据表明，除了海马外，内侧RFC还参与了长期记忆存储以进行痕量恐惧调节，这是海马依赖性的关联学习范式。在海马中观察到的MPFC之前，MPFC发生了与细胞外信号调节激酶（ERK）的训练相关激活，这表明MPFC可塑性可能不取决于海马信息的存储（或可塑性）。由于多巴胺反复证明是适当的前额叶功能所必需的，因此多巴胺D1受体活性可能会调节MPFC存储器存储。基于这些观察结果和其他观察，本提案将检验一个总体假设，即信息在前额叶皮层中长期存储是作为较高认知任务培训的直接结果。这三个具体目的是：（1）检查MPFC中长期记忆的分子相关性是否发生在痕量恐惧条件（2）中，以检查MPFC多巴胺受体在长期记忆中对痕量恐惧条件的贡献。 （3）检查记忆存储期间海马和MPFC可塑性之间的相互作用，以实现痕量恐惧调节。目前，对内存存储过程的理解不完整。对PFC存储器存储的研究对于我们对此过程的理解以及MPFC内的存储器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。由于前额叶皮层的功能通常由于神经和精神疾病的衰老而受到损害，并在脑损伤之后受到损害，因此了解该结构在长期记忆中的作用将提供信息，从而有助于为这些疾病指导治疗策略。