Delineating and testing a microcircuit model of parahippocampal phase precession

在整个海马结构中，位置细胞或网格细胞的放电活动与脑电图的θ节律（~8Hz）是相关的：当动物进入细胞的放电场时，第一个峰值到达θ振荡的后期。当动物穿过磁场时，θ振荡的后续周期中的峰值到达越来越早的阶段。尖峰“推进”贯穿整个场地。相进动是系统神经科学中研究最多的课题之一，它可能有助于将行为学习的时间尺度（发生在秒或更长时间的范围内）与突触可塑性的时间尺度（通常在毫秒范围内）相匹配。以往对相进动的研究已经形成了丰富的神经元放电现象描述和许多相进动模型。然而，相进动的机制尚不清楚。我们将尝试通过分析内嗅皮层的第三层来解决这个问题，在那里神经元表现出明显的相位进动。先前解释相位进动的尝试受到四个相互交织的问题的困扰：(1)相位进动模型通常缺乏约束；(2)大多数研究没有制定精确的微电路模型；(3)模型因此不具有很强的预测性；(4)模型通常没有经过测试，即它们在实验上是无关的。我们研究联盟的独特组成和互补的专业知识将使我们能够克服这些问题：(i)连通性分析和高分辨率记录将以前所未有的精度描绘内鼻微电路。这些数据将汇集到一个强预测性微电路模型中。（iii）因此，该模型可以进行体内和体外实验。我们的方法将使我们能够选择性地干扰相位进动，并测试其在空间记忆形成中的作用。

Throughout the hippocampal formation, the firing activity of place or grid cells and the EEG theta rhythm (~8Hz) are related: When an animal enters a cell´s firing field, the first spikes arrive at a late phase of the theta oscillation. As the animal traverses the field, the spikes in subsequent cycles of the theta oscillation arrive at earlier and earlier phases. Spikes "precess" throughout the place field. Phase precession is one of the most investigated topics in systems neuroscience and might be instrumental in matching the time scale of behavioral learning, which occurs in the range of seconds or more, to the time scales of synaptic plasticity, which are often in the range of milliseconds. Previous research on phase precession resulted in a rich description of the temporal discharge phenomenology of neurons and in numerous models of phase precession. Still the mechanism(s) underlying phase precession are unknown. We will try to solve this problem by analyzing layer 3 of the entorhinal cortex, where neurons show prominent phase precession. Previous attempts to explain phase precession suffered from four intertwined problems: (1) phase precession models are typically underconstrained, (2) most studies do not formulate precise microcircuit models, (3) models are therefore not strongly predictive, (4) models are typically not tested, i.e. they are experimentally inconsequential. The unique composition and the complementary expertise of our research consortium will allow us to overcome these problems: (i) Connectivity analysis and high-resolution recordings will delineate entorhinal microcircuits with unprecedented precision. (ii) These data will be funneled into a strongly predictive microcircuit model. (iii) Accordingly, this model can be tested in vitro and in vivo. Our approach will enable us to selectively interfere with phase precession and test its role in spatial memory formation.