Memory allocation in the hippocampus

海马体的内存分配

• 批准号: 8514400
• 负责人: Denise Jade Cai
• 金额: $ 5.38万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-01 至 2014-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8514400
• 关键词: Affect; Allatostatin; Alzheimer' s Disease; Amygdaloid structure; Behavioral; Brain; Brain region; CREB1 gene; Cells; Dementia; Drosophila genus; Environment; Exposure to; G-Protein-Coupled Receptors; Gene Expression Regulation; Hippocampus (Brain); Histones; Hour; Information Storage; Knowledge; Label; Lateral; Learning; Ligands; Mediating; Memory; Memory Disorders; Memory Loss; Memory impairment; Mus; Neurons; Patients; Phase; Play; Population; Probability; Process; Recruitment Activity; Regulation; Reporting; Role; Simplexvirus; Structure; System; Testing; Time; Training; Transgenic Mice; Transgenic Organisms; Viral; Viral Vector; Western Blotting; aging population; base; design; neuronal excitability; novel; patch clamp; time interval

DESCRIPTION (provided by applicant): Numerous studies have demonstrated the importance of CREB in memory consolidation. However, recent findings suggest that CREB also plays a key role in memory allocation. Increasing the levels of CREB increases the probability that a given neuron in the amygdala will be recruited into a memory trace, while decreasing the levels of CREB has the opposite effect. Previous results also suggest that CREB affects memory allocation by altering neuronal excitability, whereby high levels of CREB increases the intrinsic excitability of neurons in the amygdala which biases these cells towards being included in the memory trace. While there is convincing evidence that CREB and neuronal excitability are important for memory allocation in the amygdala, it is unclear whether these principles generalize to other brain regions important for memory, such as the hippocampus. I propose to directly test this hypothesis by manipulating a subpopulation of CA1 neurons with viral CREB to see if the representation is biased towards those neurons with increased CREB. Additionally, I will examine the temporal dynamics of CREB activation and neuronal excitability in CA1 following acquisition of a context memory using Western blot analysis and whole cell patch recording, respectively. Lastly, I will examine the co-allocation of two memories with transgenic TetTag mice, which can label activated neurons at 2 different time points. My prediction is that if CREB biases memory allocation, then increased CREB activation induced by one hippocampus-dependent memory should bias the allocation of a second memory to many of the same neurons recruited to store the first memory. Our previous studies in the lateral amygdala pioneered the field of memory allocation. While this field has been very exciting, it has been exclusively limited to the amygdala and for this field to move forward, it is essential that we can generalize our findings to other brains structures and memory types. The results from these proposed studies will give us a better idea of how memory allocation processes affect the integration and storage of information. With this knowledge, we can better develop targeted treatments for memory disorders, including Alzheimer¿s disease, as we already know there is aberrant CREB-mediated gene regulation in this population.

描述（由申请人提供）：许多研究表明CREB在记忆巩固中的重要性。然而，最近的研究结果表明，CREB在内存分配中也起着关键作用。增加CREB的水平会增加杏仁核中给定神经元被招募到记忆痕迹中的概率，而降低CREB的水平则会产生相反的效果。先前的结果还表明，CREB通过改变神经元的兴奋性来影响记忆分配，由此高水平的CREB增加杏仁核中神经元的内在兴奋性，这使这些细胞偏向于被包括在记忆痕迹中。虽然有令人信服的证据表明CREB和神经元兴奋性对杏仁核中的记忆分配很重要，但尚不清楚这些原则是否适用于对记忆很重要的其他大脑区域，如海马体。我建议直接测试这一假设，操纵一个亚群的CA1神经元与病毒CREB，看看代表性是偏向于那些神经元CREB增加。此外，我将研究CREB激活和神经元兴奋性的时间动态CA1收购后的上下文记忆使用Western印迹分析和全细胞补丁记录，分别。最后，我将用转基因TetTag小鼠研究两种记忆的共同分配，这种小鼠可以在2个不同的时间点标记激活的神经元。我的预测是，如果 CREB偏向记忆分配，那么由一个依赖于校园的记忆诱导的CREB激活增加应该会偏向第二个记忆分配给许多被招募来存储第一个记忆的相同神经元。 我们先前对外侧杏仁核的研究开创了记忆分配领域的先河。虽然这一领域一直非常令人兴奋，但它一直仅限于杏仁核，为了使这一领域向前发展，我们必须能够 将我们的发现推广到其他大脑结构和记忆类型。这些研究的结果将使我们更好地了解内存分配过程如何影响信息的整合和存储。有了这些知识，我们可以更好地开发针对记忆障碍的靶向治疗方法，包括阿尔茨海默病，因为我们已经知道在这个人群中存在异常的CREB介导的基因调控。