Hebb Marr Networks the Hippocampus and Spatial Memory

描述（由申请人提供）：编码、存储、检索和 情景记忆或其他形式的记忆的巩固， 分布在多个区域的大型神经群体的扩展交互 大脑区域。我们建议对 在一个紧密联系的系统内与记忆相关的神经集成相互作用， 在记忆过程中起重要作用的大脑区域。这些区域包括 海马、杏仁核、内侧前额叶皮质、背侧和腹侧纹状体 和黑质/腹侧被盖。我们主要关注的是 自发记忆痕迹再激活，在操作上定义为 神经生理学术语，如神经活动模式的重建 与最近的经验相匹配。序列检索 这种先前编码的模式可以被理解为神经反射， 情景记忆长期以来，离线检索一直被提出来帮助 记忆巩固的过程。在此之前，我们建立了几个重要的 这一过程的基本特征：它发生在海马 和一些新皮层神经系统;它以压缩的形式再现了 编码经验的短期时间顺序;它在一段时间内最强 在经历后的30-60分钟内，但至少可以观察24小时 小时后对这项建议特别重要的是，我们认为， 海马记忆痕迹的再激活主要在特定的 神经生理事件，海马尖波。尖锐的波浪 提出了反映海马神经元会聚的理论依据 关联网络到吸引子（即，存储的存储器）状态。这项建议 解决了一些关键的未解之谜：记忆的重新激活 新皮质和皮质下结构中的痕迹， 海马体？有没有一个新皮层或皮层下 在尖锐波中的可塑性海马再激活依赖于NMDA吗 编码过程中的受体激活？激活过程是否通过以下方式增强 积极或消极的强化，它是否与发射相互作用， 多巴胺神经元的方式，可能有助于学习路线，以奖励？做 局部药物应用（例如，海马体或杏仁核）， 促进或削弱记忆巩固，影响再激活过程？ 这种分析需要大规模并行记录方法，我们有 开发的技术，将使同时记录约150-200 单个神经元分布在多个结构中， 啮齿动物这些研究应该阐明神经生理机制， 记忆检索和巩固，并协助理解缺陷， 这一过程发生在正常和病理性衰老等条件下， 脑外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.