Temporal Organization of Memory in the Hippocampus

描述(由申请人提供)：情景记忆的特点是我们能够记住事件发生的空间和时间背景。有大量证据表明，海马神经元的活动反映了空间的表征，但直到最近，人们对海马神经元是否或如何编码时间知之甚少。然而，我们最近的研究表明，海马神经元的活动提供了一个有助于记忆的时间背景信号。此外，现在有证据表明，海马神经元--称为时间细胞--在时间延长的体验中的特定时刻发生放电，类似于在空间延长的环境中与特定位置相关的海马区神经元放电。这项拟议的研究将探索由海马体系统和前额叶皮质进行的时间表征的本质。我们将检验这样一个假设，即时间单元的关键属性与位置单元的关键属性相似。通过多个区域的同时记录，我们还将检验这样一个假设，即时间细胞与内侧内嗅皮层和前额叶皮质的时间周期表征平行，以消除重叠经验的歧义。使用麝香酚和光学沉默方法，我们将进一步检验这一假说，即海马区的时间编码取决于内侧内嗅觉皮质，以及海马区时间细胞消除重叠经验的能力取决于前额叶皮质。这些研究将挑战流行的观点，即海马体系统致力于空间导航，并促进我们对该系统如何在时空背景下表示事件的理解。

DESCRIPTION (provided by applicant): Episodic memory is characterized by our ability to remember the spatial and temporal context in which events occur. There is substantial evidence that the hippocampal neuronal activity reflects a representation of space but, until recently, little was known about whether or how the hippocampal neurons encode time. However, recent studies by us have shown that hippocampal neuronal activity provides a temporal context signal that contributes to memory. In addition there is now evidence that hippocampal neurons - called time cells - fire during particular moments in a temporally extended experience, similar to hippocampal place cells that fire associated with particular locations in a spatially extended environment. The proposed studies will explore the nature of temporal representation by the hippocampal system and prefrontal cortex. We will test the hypothesis that key properties of time cells are analogous to those of place cells. By simultaneous recordings in multiple areas, we will also test the hypothesis that time cells are paralleled by a periodic representation of time in the medial entorhinal cortex and prefrontal cortex representation that disambiguates overlapping experiences. Using both muscimol and optical silencing methods, we will further test the hypothesis that temporal coding in the hippocampus depends on the medial entorhinal cortex, and that the ability of hippocampal time cells to disambiguate overlapping experiences depends on the prefrontal cortex. These studies will challenge the prevalent view that the hippocampal system is dedicated to spatial navigation and advance our understanding of how this system represents events in their spatiotemporal context.