Cortico-Hippocampal Mechanisms of Context Memory

情境记忆的皮质-海马机制

• 批准号: 9916823
• 负责人: Jelena Radulovic
• 金额: $ 10.83万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916823
• 关键词: Acids; Affect; Affective Symptoms; Anterior; Area; Bypass; Cells; Cognition Disorders; Cognitive deficits; Complement; Cre driver; Data; Development; Dorsal; ERG gene; Electrophysiology (science); Episodic memory; Fright; Genetic; Glutamates; Hippocampus (Brain); Immediate-Early Genes; Immunohistochemistry; Impairment; Individual; Mediating; Memory; Mental disorders; Modeling; Molecular; Mood Disorders; Mus; N-Methyl-D-Aspartate Receptors; Neocortex; Neuroanatomy; Neurobehavioral Manifestations; Neurons; Outcome; Output; Pathway interactions; Patients; Pharmacology; Play; Population; Process; RBP4 gene; Research; Retrieval; Rodent; Role; Signal Transduction; Stress; System; Testing; Tetanus Helper Peptide; Time; Work; base; behavioral study; cognitive function; conditioned fear; design; designer receptors exclusively activated by designer drugs; experience; experimental study; long term memory; memory consolidation; memory encoding; memory process; memory retrieval; neocortical; nervous system disorder; novel; optogenetics; receptor; receptor function; theories; transmission process

ABSTRACT Episodic memories, particularly those associated with stressful experiences, often persist throughout a lifetime. While extensive research has helped us to better understand the hippocampal mechanisms mediating the formation of episodic memories, the role of the cortex is less well understood. Our project seeks to establish the contribution of the retrosplenial cortex (RSC), and its interactions with the dorsal hippocampus (DH), to the encoding, consolidation, and retrieval of contextual fear-provoking memories. We propose that RSC, by integrating dorsohippocampal (DH) inputs, plays a principal role in the processing of contextual memories from the earliest stages of memory encoding to remote retrieval, but that RSC, rather than DH, is the gateway of information to other parts of the neocortex. We also posit that three distinct DH-RSC projections contribute to the formation, recent, and remote retrieval of context memories, whereas layer 5 RSC neurons contribute to long-term memory consolidation. Our approaches will consist of conditional genetic and chemogenetic manipulations of individual RSC neuronal populations as well as DH-RSC projections. This will be complemented by optogenetic-electrophysiological approaches of the functional neuroanatomy of DH-RSC projections and RSC layer-specific analyses of immediate early gene responses related to memory. Understanding the molecular and circuit mechanisms of RSC function as they relate to memory will inform the development of novel treatment approaches for cognitive deficits in patients suffering from neurological and psychiatric disorders. Ideally, our findings will identify cortical pathways whose stimulation can bypass the requirement for the hippocampus in memory formation and can thus serve as a novel treatment option.

抽象的 情景记忆，尤其是那些与压力经历相关的记忆，通常会持续一生。 虽然广泛的研究帮助我们更好地了解海马机制介导 对于情景记忆的形成，皮层的作用还不太了解。我们的项目旨在建立 压后皮质 (RSC) 的贡献及其与背侧海马 (DH) 的相互作用 对引发恐惧的记忆进行编码、巩固和检索。我们建议 RSC，通过 整合背海马（DH）输入，在上下文记忆的处理中起着主要作用 记忆编码到远程检索的最早阶段，但 RSC，而不是 DH，是 新皮质其他部分的信息。我们还假设三个不同的 DH-RSC 预测有助于 上下文记忆的形成、最近和远程检索，而第 5 层 RSC 神经元则有助于 长期记忆巩固。我们的方法将包括条件遗传学和化学遗传学 单个 RSC 神经元群体的操作以及 DH-RSC 预测。这将是 DH-RSC 功能神经解剖学的光遗传学-电生理学方法作为补充 与记忆相关的早期基因反应的预测和 RSC 层特异性分析。 了解 RSC 功能与记忆相关的分子和电路机制将为 开发新的治疗方法来治疗患有神经系统疾病和认知障碍的患者的认知缺陷 精神疾病。理想情况下，我们的研究结果将确定其刺激可以绕过的皮质通路 海马体在记忆形成中的需求，因此可以作为一种新的治疗选择。