Hebb Marr Networks the Hippocampus and Spatial Memory

描述(申请人提供)：编码、存储、检索和 巩固情节记忆或其他形式的记忆涉及到时间上的 分布在多个区域的大型神经种群的扩展相互作用 大脑区域。我们建议进行一项神经生理学分析 在一个紧密相连的系统内与记忆相关的神经系综相互作用 在记忆过程中很重要的大脑区域。这些地区包括 海马体、杏仁核、内侧前额叶皮质、背侧和腹侧纹状体 黑质/腹侧被盖。我们的主要关注点是 自发记忆轨迹重新激活，在操作上定义为 神经生理学术语：神经活动模式的重建 这与最近的经验所强加的情况相吻合。检索序列 这种先前编码的图案的神经反射可以被理解为 情节记忆。长期以来，人们一直建议离线检索以帮助 记忆巩固的过程。之前，我们建立了几个重要的 这一过程的基本特征：它在海马区连贯地发生 和一些新皮质神经集合；它以压缩的形式重建 编码经验的短期时间顺序；在 30-60分钟后体验一次，但至少可观察24分钟 几个小时后。对这项提议特别重要的是，我们观察到 海马区记忆踪迹的重新激活主要在特定的 神经生理学事件，海马区尖波。尖峰的海浪已经 提出了反映海马区会聚的理论依据 联想网络到吸引子(即，存储的记忆)状态。这项建议 回答了一些关键的悬而未决的问题：是记忆的重新激活 新皮质和皮质下结构中的痕迹由 海马体？有增强的新皮质或皮质下窗口吗？ 尖浪中的可塑性？海马区的重新激活依赖NMDA吗 编码过程中的受体激活？重新激活的过程是否因为 积极的还是消极的强化以及它是否与激发 以一种可能有助于学习途径的方式来奖励多巴胺神经元？做 局部药物应用(例如，在海马体或杏仁核)，这 促进或损害记忆巩固，影响重新激活过程？ 这样的分析需要大规模的并行记录方法，我们有 开发的技术可实现约150-200的同时记录 在未麻醉状态下，单个神经元分布在多个结构上，表现为 啮齿动物。这些研究应该澄清神经生理学机制。 记忆的提取和巩固，并帮助理解记忆缺陷 这一过程发生在正常和病理性衰老等条件下， 脑创伤、发育障碍和药物滥用。

DESCRIPTION (provided by the applicant): The encoding, storage, retrieval and consolidation of either episodic or other forms of memory involves temporally extended interactions of large neural populations distributed over multiple brain regions. We propose to conduct a neurophysiological analysis of memory-related neural ensemble interactions within a closely linked system of brain regions that are important in mnemonic processes. These regions include hippocampus, amygdala, medial prefrontal cortex, dorsal and ventral striatum and substantia nigra/ventral tegmentum. Our main focus is the process of spontaneous memory trace reactivation, operationally defined in neurophysiological terms as the reestablishment of neural activity patterns that match those that were imposed by recent experience. Retrieval of sequences of such previously encoded patterns can be understood as a neural reflection of episodic memory. Off-line retrieval has long been proposed to assist in the process of memory consolidation. Previously, we established several important basic characteristics of this process: it occurs coherently among hippocampal and some neocortical neural ensembles; it recreates, in a compressed form, the short-term temporal order of encoded experiences; 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 for this proposal is our observation that hippocampal memory trace reactivation is expressed primarily during a specific neurophysiological event, the hippocampal sharp-wave. Sharp-waves have been proposed on theoretical grounds to reflect the convergence of hippocampal associative networks onto attractor (i.e., stored memory) states. This proposal addresses a number of key unanswered questions: Is reactivation of memory traces in neocortical and subcortical structures coordinated by the hippocampus? Is there a window of enhanced neocortical or subcortical plasticity during sharp-waves? Is hippocampal reactivation dependent on NMDA receptor activation during encoding? Is the reactivation process potentiated by positive or negative reinforcement and does it interact with the firing of dopamine neurons in a manner that may assist in learning routes to reward? Do localized drug applications (e.g., in the hippocampus or amygdala), which facilitate or impair memory consolidation, affect the reactivation process? Such analyses require large scale parallel recording methods, and we have developed technology that will enable simultaneous recording from about 150-200 single neurons distributed over multiple structures in unanesthetized, behaving rodents. These studies should clarify the neurophysiological mechanisms of memory retrieval and consolidation, and assist in understanding deficits in this process that occur under conditions such as normal and pathological aging, brain trauma, developmental disorders and substance abuse.