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（由申请人提供）：大量研究证明了 CREB ​​在记忆巩固中的重要性，然而，最近的研究结果表明 CREB ​​在记忆分配中也发挥着关键作用，增加 CREB ​​水平会增加杏仁核中特定神经元的可能性。会被招募到记忆痕迹中，而降低 CREB ​​水平会产生相反的效果，之前的结果也表明 CREB ​​通过改变神经兴奋性来影响记忆分配，因此高水平的 CREB ​​会增加内在的记忆分配。虽然有令人信服的证据表明 CREB ​​和神经兴奋性对于杏仁核的记忆分配很重要，但尚不清楚这些原理是否适用于对记忆轨迹重要的其他大脑区域。我建议通过用病毒 CREB ​​操纵 CA1 神经元亚群来直接检验这一假设，看看该表征是否偏向于那些具有增加 CREB ​​的神经元。将分别使用蛋白质印迹分析和全细胞贴片记录获取上下文记忆后，检查 CREB ​​激活和神经兴奋性的时间动态。最后，我将检查转基因 TetTag 小鼠的两个记忆的共同分配。我的预测是，如果在两个不同的时间点标记激活的神经元。 CREB ​​会偏向记忆，然后，由一个海马依赖性记忆引起的 CREB ​​激活的增加应该会使第二个记忆的分配偏向于许多被招募来存储第一个记忆的相同分配神经元。我们之前在外侧杏仁核中的研究开创了记忆分配领域。虽然这个领域非常令人兴奋，但它仅限于杏仁核，为了使这个领域向前发展，我们必须能够做到这一点。 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记忆分配过程如何影响信息的整合和存储。有了这些知识，我们就可以更好地开发针对记忆的针对性治疗方法。疾病，包括阿尔茨海默病¿正如我们所知，该人群中存在异常的 CREB ​​介导的基因调控。 公共健康相关性：阿尔茨海默病 (AD) 是老年人群中最常见的痴呆症，记忆障碍是其主要特征。有强有力的证据表明，这些患者的大脑中 CREB ​​调节异常，这可能与其有关。这些拟议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，我们就可以更好地开发针对记忆障碍（包括阿尔茨海默病）的治疗方法。