Cortico-Hippocampal Mechanisms of Context Memory

摘要 情节记忆，特别是那些与紧张经历相关的记忆，通常会持续一生。 虽然广泛的研究帮助我们更好地理解了海马体机制 在情景记忆的形成过程中，大脑皮层的作用还不是很清楚。我们的项目旨在建立 脾后皮质(RSC)及其与背侧海马区(DH)的相互作用 对情景恐惧记忆进行编码、巩固和检索。我们建议RSC，通过 整合背海马区(Dh)的输入，在加工来自 从记忆编码到远程提取的最早阶段，但RSC，而不是DH，是 信息传到大脑皮层的其他部分。我们还假设三个不同的DH-RSC投影有助于 背景记忆的形成、最近和远程提取，而第5层RSC神经元参与 长期记忆巩固。我们的方法将包括条件遗传和化学遗传 个体RSC神经元群体的操作以及DH-RSC投射。这将是 辅之以光遗传-电生理方法研究双侧视网膜神经干细胞的功能解剖 与记忆相关的即刻早期基因反应的投影和RSC层特定分析。 了解RSC与记忆相关的分子和电路机制将有助于 神经精神障碍患者认知功能障碍治疗新方法的开发 精神障碍。理想情况下，我们的发现将确定皮层通路，其刺激可以绕过 在记忆形成中对海马体的需求，因此可以作为一种新的治疗选择。

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.