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记住事件发生的空间和时间背景的能力。有大量证据表明，海马体神经元的活动反映了空间的表征，但直到最近，人们对海马体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，海马体神经元活动提供了一种有助于记忆的时间背景信号。此外，现在有证据表明，海马体神经元——被称为时间细胞——在时间扩展体验的特定时刻放电，类似于海马体位置细胞在空间扩展环境中的特定位置放电。提出的研究将探讨海马系统和前额叶皮层的时间表征的本质。我们将检验时间细胞的关键特性与位置细胞相似的假设。通过在多个区域同时记录，我们还将验证时间细胞在内嗅皮层和前额叶皮层的周期性时间表征中是平行的假设，从而消除重叠经验的模糊性。使用muscimol和光学沉默方法，我们将进一步验证海马体的时间编码取决于内侧内嗅皮层的假设，以及海马体时间细胞消除重叠经验的能力取决于前额叶皮层的假设。这些研究将挑战海马体系统致力于空间导航的流行观点，并推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. PUBLIC HEALTH RELEVANCE: Our understanding of cognitive disorders, and the eventual development of treatments, depends crucially upon an understanding of the cognitive and neural mechanisms that underlie normal cognition; for example, abnormal thought patterns in schizophrenia, as well as other cognitive disorders, reflects an underlying disorganization of the neural machinery that stores and retrieves memories of our everyday experiences. The proposed work will pioneer a new understanding about how memories are represented in neural circuitry and about how neural representations are organized to guide our retrieval of memories in daily life. Because the hippocampus and adjacent cortical areas are compromised in multiple major mental disorders, an understanding the functional circuitry of these areas is particularly important.