Memory allocation in the hippocampus

海马体的内存分配

• 批准号: 8316596
• 负责人: Denise Jade Cai
• 金额: $ 5.22万
• 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 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316596
• 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. PUBLIC HEALTH RELEVANCE: Alzheimer's disease (AD) is the most common form of dementia in the aging population and memory impairment is the principle defining feature. There is strong evidence that these patients have an aberrant regulation of CREB in the brain, which could be related to the memory loss. The results from these proposed studies will give us a better idea of how CREB affects the integration and storage of information. With this knowledge, we can better develop targeted treatments for memory disorders, including Alzheimer's disease.

描述（由适用提供）：大量研究证明了CREB在记忆合并中的重要性。但是，最近的发现表明CREB在记忆分配中也起着关键作用。提高CREB的水平会增加杏仁核中给定神经元的概率，而降低CREB的水平具有相反的效果。先前的结果还表明，CREB通过改变神经元兴奋会影响记忆分配，从而高水平的CREB增加了杏仁核中神经元的内在兴奋，从而使这些细胞偏向于记忆痕迹中。尽管有令人信服的证据表明，Creb和神经元兴奋对于杏仁核中的记忆分配很重要，但尚不清楚这些原则是否将其推广到其他对记忆很重要的大脑区域，例如海马。我建议通过操纵病毒CREB的CA1神经元的亚群来直接检验这一假设，以查看该表示是否偏向于CREB增加的神经元。此外，我将分别使用Western印迹分析和全细胞斑块记录在获取上下文记忆后，将检查CA1中CREB激活和神经元兴奋的暂时动力学。最后，我将检查两个记忆与转基因苔藓小鼠的共同分配，这些记忆可以在2个不同的时间点标记激活的神经元。我的预测是 CREB偏向内存分配，然后增加了一个由海马依赖性记忆引起的CREB激活，应该将第二个内存的分配偏向于募集的许多相同神经元以存储第一个内存。我们先前在杏仁核外侧的研究率先进行了内存分配领域。尽管该领域非常令人兴奋，但它仅限于杏仁核，而对于该领域的前进，我们必须可以 将我们的发现概括为其他大脑结构和内存类型。这些拟议的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集成和存储。有了这些知识，我们可以更好地为包括阿尔茨海默氏病在内的记忆障碍的有针对性的治疗方法开发，因为我们已经知道，在该人群中存在异常的CREB介导的基因调节。 公共卫生相关性：阿尔茨海默氏病（AD）是人口老龄化和记忆障碍中最常见的痴呆形式，是定义特征的原则。有充分的证据表明，这些患者对大脑中的CREB有异常的调节，这可能与记忆丧失有关。这些拟议的研究的结果将使我们更好地了解CREB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包括阿尔茨海默氏病在内的记忆障碍的有针对性治疗方法。