Hippocampal impact on prefrontal cortex: basic mechanisms of memory consolidation

记忆形成是所有高等神经系统的关键功能，对神经元可塑性的细胞和分子机制的研究非常深入。在网络层面，我们的知识还不够先进。研究得最好的模型系统之一是啮齿动物内嗅-海马系统的空间记忆形成，在那里我们对空间调谐的spike模式及其通过不同类型的网络振荡的组织有了很多了解。在更大的范围内，记忆的长期巩固涉及海马体和新皮质区域，特别是前额皮质之间的协调活动。然而，这种相互作用的细胞和网络机制尚不清楚。我们想探索从海马到前额叶网络的信息传递，重点是可塑性。我们认为从海马体到前额叶网络的信号是强烈的状态依赖性。因此，我们将在体外和体内诱导不同模式的海马活动，并测量它们对前额叶神经元的影响。然后，我们将进入网络水平，观察前额叶皮层的多细胞活动模式，并询问这些模式如何受到海马输入信号的影响。为了研究海马诱导的可塑性，将使用LTP/ ltd范式刺激前额叶皮层的输入。将在蜂窝和网络级别测量其影响。最后，活体动物实验将揭示两个区域振荡网络之间耦合的状态依赖性。为了进行因果分析，将使用电和光遗传学方法专门操纵海马传入事件。总之，我们的实验将阐明海马体网络如何以状态和活动依赖的方式影响前额叶活动模式。因此，它们将对目前记忆巩固的概念作出重要贡献。

Memory formation is a key function of all higher nervous systems, and research on cellular and molecular mechanism of neuronal plasticity is highly advanced. At the level of networks, our knowledge is still less advanced. One of the best studied model systems is spatial memory formation in the entorhinal-hippocampal system of rodents, where we know much about spatially tuned spike patterns and their organization by different types of network oscillations. On a larger scale, long-term consolidation of memories involves coordinated activity between the hippocampus and neocortical areas, especially the prefrontal cortex. The cellular and network mechanisms of this interaction are, however, unknown. We want to explore information transfer from hippocampal to prefrontal networks, with focus on plasticity. We suggest that signaling from hippocampal to prefrontal networks is strongly state-dependent. We will therefore induce different patterns of hippocampal activity in vitro and in vivo, and measure their impact on prefrontal neurons. We will then proceed to the network level and observe multicellular activity patterns in the prefrontal cortex, asking how these patterns are affected by hippocampal input signals. In order to study hippocampus-induced plasticity, inputs to the prefrontal cortex will be stimulated with LTP/LTD-paradigms. The impact will be measured both at the cellular as well as at the network level. Finally, experiments in living animals shall reveal the state-dependence of coupling between oscillating networks in both regions. For causal analysis, hippocampal afferents will be specifically manipulated using electrical and optogenetic methods. Together, our experiments shall elucidate how hippocampal networks affect prefrontal activity patterns in a state- and activity-dependent manner. They shall, therefore, make an important contribution to present concepts of memory consolidation.