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）：大量研究已经证明了CREB在记忆巩固中的重要性。然而，最近的研究结果表明，CREB在记忆分配中也起着关键作用。增加CREB的水平会增加杏仁核中特定神经元被招募到记忆痕迹的可能性，而降低CREB的水平则会产生相反的效果。先前的研究结果还表明，CREB通过改变神经元的兴奋性来影响记忆分配，因此，高水平的CREB增加了杏仁核神经元的内在兴奋性，使这些细胞倾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的记忆分配很重要，但尚不清楚这些原理是否适用于其他对记忆重要的大脑区域，如海马体。我建议通过操纵具有病毒CREB的CA1神经元亚群来直接测试这一假设，看看这种表现是否偏向于那些具有增加CREB的神经元。此外，我将分别使用Western blot分析和全细胞贴片记录来研究获得上下文记忆后CA1中CREB激活和神经元兴奋性的时间动态。最后，我将研究两种记忆与转基因TetTag小鼠的共同分配，它可以标记两个不同时间点的激活神经元。我的预测是