Identification and Manipulation of Active Memory Circuits

主动记忆电路的识别和操作

• 批准号: 8392655
• 负责人: Kartik Ramamoorthi
• 金额: $ 3.67万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392655
• 关键词: Antibodies; Automobile Driving; Behavioral; Biochemical; Brain; Cell physiology; Cells; Genetic; Goals; Hippocampus (Brain); Image; Impairment; In Vitro; Intention; Label; Lead; Learning; Memory; Molecular; Neurologic; Neurons; Neurosciences; Population; Property; Proteins; Reporter; Reporting; Research Proposals; S cerevisiae SWI3 protein; Sensory; Staining method; Stains; Structure; System; Testing; Therapeutic; Time; conditioned fear; design; electrical property; experience; flexibility; hippocampal pyramidal neuron; in vivo; information processing; interest; memory recall; novel; promoter; research study; tool; transcription factor

DESCRIPTION (provided by applicant): A fundamental goal in neuroscience is to understand mechanisms underlying the ability to create memories from sensory experience. While large structures such as the hippocampus are known to be critical for certain types of learning, memories are ultimately thought to be represented in sparsely distributed neuronal ensembles within these larger structures. Currently, there are no tools that allow for the identification and manipulation of these ensembles, which has limited our understanding of the molecular and cellular processes underlying learning and memory. We have previously reported that the activity regulated transcription factor Npas4 is selectively induced in a sparse population of CA3 hippocampal neurons by contextual learning. Furthermore, expression of Npas4 in the hippocampus is necessary for contextual memory formation. The goal of this research proposal is to determine if neurons expressing Npas4 following contextual learning comprise a memory circuit in CA3. Using a genetic reporter that is activated by Npas4, we will manipulate the electrical and biochemical properties of neurons expressing Npas4 following contextual learning, in order to test whether this population represents a neuronal ensemble required for information processing and memory recall. These experiments will provide unprecedented access to an active neuronal ensemble, which may lead to a greater understanding of the mechanisms underlying learning and memory. PUBLIC HEALTH RELEVANCE: The goal of this proposal is to examine the mechanism of memory formation. The vast majority of neurological orders lead to profound impairments in learning and memory. By understanding the basic mechanisms of memory formation we can begin to develop therapeutic strategies to reverse these impairments.

描述（由申请人提供）：神经科学的基本目标是了解从感官体验创造记忆力的能力的基础机制。尽管已知海马等大型结构对于某些类型的学习至关重要，但最终认为记忆在这些较大的结构内被认为是稀疏分布的神经元集合所代表的。当前，没有任何工具可以进行身份​​识别和 对这些合奏的操纵，这限制了我们对学习和记忆基础的分子和细胞过程的理解。我们先前已经报道说，通过上下文学习，在CA3海马神经元的稀疏种群中选择性诱导活性调节的转录因子NPAS4。此外，对于上下文记忆形成，必须在海马中表达NPAS4。该研究建议的目的是确定在上下文学习之后表达NPAS4的神经元是否包含CA3中的内存电路。使用NPAS4激活的遗传记者，我们将操纵在上下文学习后表达NPAS4的神经元的电和生化特性，以测试该人群是否代表信息处理和记忆回忆所需的神经元集合。这些实验将为主动神经元合奏提供前所未有的访问，这可能会导致对学习和记忆的机制有更深入的了解。 公共卫生相关性：该提案的目的是检查记忆形成的机制。绝大多数神经秩序导致学习和记忆力方面的严重损害。通过了解记忆形成的基本机制，我们可以开始制定治疗策略来扭转这些障碍。