Hebb Marr Networks the Hippocampus and Spatial Memory

超出空间 提供了 由正常和病理性衰老、脑外伤、发育性 精神障碍、药物滥用和创伤经历，如性虐待或战斗， 健康问题。对记忆的大脑机制的理解和动物模型的发展 在应用研究中使用，对于最终开发有效的治疗干预措施至关重要， 紊乱记忆的编码、储存、提取和巩固都涉及到时间上扩展的相互作用 分布在大脑中的大量神经群。我们提出了神经生理学分析， 在大脑区域的链接系统内与记忆相关的神经集成相互作用， 记忆过程，包括海马和邻近的新皮层关联区，边缘皮层，腹侧 纹状体和黑质/腹侧被盖。我们主要关注的是自发记忆追踪的过程 检索，定义为自发重新建立神经活动模式， 这个过程可以通过分析神经元之间的统计相互作用来研究。 检索阶段期间的集合与编码期间观察到的集合相匹配。这种离线检索 似乎在记忆巩固过程中起着关键作用。我们已经建立了几个重要的基础 这一过程的特点：它发生在海马和新皮层区域之间的连贯性;它重新创造，在一个 压缩形式，编码经验的短期时间顺序;在30-60 但至少24小时后才能观察到。特别重要的是我们观察到 海马记忆痕迹的再激活主要在特定的神经生理事件中表达， 海马“锐波”（SPW）。SPW已经在理论上被提出来反映以下收敛性： 海马关联网络存储的记忆状态，我们的研究结果确定SPW作为记忆读出 海马体中的事件。关于这些事件的动态， 海马以及SPW传输的信息如何与新皮层动力学相互作用，以建立海马- 新皮层和其他大脑回路中的独立长期记忆。拟议的研究将同时推进 我们对记忆生物学的理解，并导致精确的，定量的动物模型的发展， 用于药物开发和其他治疗研究。特别是，几项拟议的研究是 与理解创伤后应激障碍中的“闪回”记忆等现象有直接关系。

EXCEED THE SPACE PROVIDED. Learning and memory disorders resulting from normal and pathological aging, brain trauma, developmental disorders, substance abuse, and traumatic experiencessuch as sexual abuse or combat, represent a major public health concern. The development of an understanding of brain mechanisms of memory and of animal models for use in applied studies, is critical to the ultimate development of effective theraputic interventions for these disorders. The encoding, storage, retrieval and consolidation of memory involves temporally extended interactions of large neural populations distributed widely over the brain. We propose the neurophysiological analysis of memory-related neural ensemble interactions within a linked system of brain regions that are important in mnemonic processes, including hippocampus and adjacent neocortical association areas, limbic cortex, ventral striatum and substantia nigra/ventral tegmentum. Our main focus is the process of spontaneous memory trace retrieval, defined as the spontaneous re-establishment of neural activity patterns that match those that were imposed by recent experience.This process can be studied by analyzing how statistical interactions among neural ensembles during the retrieval phase match those that were observed during encoding. Such off-line retrieval appears to play a critical role in the process of memory consolidation. We have established several important basic characteristics of this process: it occurs coherently among hippocampal and neocortical regions; it recreates,in a compressed form, the short-term temporal order of encodedexperiences;it is strongest during a period of 30-60 minutes after an experience, but can be observed at least 24 hours later. Of particular importance is our observation that hippocampal memory trace reactivation is expressedprimarily during a specific neurophysiological event, the hippocampal 'sharp-wave' (SPW). SPWs have been proposed on theoretical grounds to reflectthe convergence of hippocampal associative networks onto stored memory states, and our findings identify SPWs as memory readout events in the hippocampus. Much remains to be learned about the dynamics of these events within the hippocampus and how SPWtransmitted information interacts with neocortical dynamics to establish hippocampus- independent long-term memories in neocortical and other brain circuits. The proposed studies will both advance our understanding of the biology of memory and lead to the development of precise, quantitative animal models for use in drug developmentand other theraputic investigations. In particular, several of the proposed studies are of direct relevanceto understanding phenomena such as 'flashback' memory in post-traumatic stress disorder.