A neuronal code for extended time in the hippocampal-entorhinal circuitry

海马-内嗅回路中延长时间的神经元代码

• 批准号: 8630825
• 负责人: Jill K Leutgeb
• 金额: $ 36.71万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-02-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630825
• 关键词: Address; Alzheimer' s Disease; Animals; Area; Behavior; Behavioral; Biological Neural Networks; Brain; Brain region; Cells; Code; Data; Disease; Environment; Episodic memory; Event; Foundations; Functional disorder; Future; Hippocampal Formation; Hippocampus (Brain); Hour; Human; Lateral; Lesion; Location; Measures; Medial; Memory; Memory Loss; Mental disorders; Neurodegenerative Disorders; Neurons; Pathology; Patients; Pattern; Population; Post-Traumatic Stress Disorders; Publishing; Radial; Rattus; Retrieval; Rodent; Schizophrenia; Structure; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Theoretical model; Time; Traumatic Brain Injury; Update; arm; awake; base; behavior test; entorhinal cortex; experience; long term memory; memory process; nervous system disorder; novel; public health relevance; relating to nervous system; repaired; research study; time interval; treatment strategy

PROJECT SUMMARY/ABSTRACT The hippocampal formation is critical for the formation and retrieval of autobiographical memories, which consist of information about what happened when and where. It is known how objects, context and space (what, where) are represented in the hippocampus and it has recently been described that time (when events occur) on a scale of seconds to minutes is represented by the sequential activation of hippocampal cells. On a longer time scale, a time-varying neural code has previously been shown by theoretical models to be suitable for estimating the recency of a remembered event. In recently published results and results presented as preliminary data, we identify a novel, time-varying hippocampal neural code that can represent how long ago an event occurred on a time scale of hours and days. Our data first identified that the neuronal firing patterns of CA1 cells are characterized by a monotonic accumulation of rate differences as a function of time between experiences. However, we demonstrate that stored information does not simply deteriorate in the CA1 area, but that the code for time can co-exist with reliable coding for other aspects of an event, such as the spatial location or the context. We also found that CA3 contains an exquisitely precise code for context and space that does not vary over time. New preliminary data show an effect in CA2 that is opposite of CA3. CA2 cells represent elapsed time but no information about context. Based on these findings, we hypothesize that the neuronal code for extended time is combined with spatial and contextual information in the CA1 cell population to guide behavior in which the recency of a previous event is remembered. Using a combination of behavioral testing and single-unit recordings in awake behaving rodents, this hypothesis is tested in three aims that: (1) determine whether the neuronal code for extended time intervals is generated in the hippocampal CA2 neural network, (2) determine whether the input from the hippocampal CA3 subregion is necessary for maintaining the stable memory coding component in the CA1 neural network over hours and days, and (3) determine whether a time-varying neural code in hippocampal CA1 and CA2 subregions is correlated with remembering "how long ago". The first two aims address how different subregions contribute to the time-varying and stable components of the neural code. In addition to defining the function of CA2 for temporal coding and the function of CA3 in enabling stable memory representations, we will also ask whether the entorhinal cortex can represent time on an extended scale and is thus a brain region in which temporal coding over a large range of scales can be found. In the third aim, we will use a behavioral task in which it has been shown that rats remember "how long ago" over extended time periods. We will measure the similarity of activity patterns in place cell populations between two time points and determine whether the change in neuronal firing patterns corresponds to the rat's estimate of elapsed time. Taken together, these studies will be important for understanding the neural network mechanisms for long-term memory stability and temporal event coding in the brain structures that support episodic memory. Understanding the key mechanisms for memory processing will guide efforts to repair circuit dysfunction in psychiatric, neurological, and neurodegenerative diseases.

项目总结/摘要 海马结构对于自传体记忆的形成和提取至关重要，自传体记忆包括 有关何时何地发生的事情的信息。它是已知的对象，上下文和空间（什么，在哪里）是如何 最近有人描述，以秒为单位的时间（事件发生时） 以海马细胞的顺序激活表示。在较长的时间尺度上， 神经代码先前已经被理论模型证明适合于估计记忆的新近性。 活动在最近发表的结果和结果作为初步数据，我们确定了一个新的，随时间变化的 海马神经编码可以代表事件发生的时间，以小时和天为单位。我们 数据首次发现，CA 1细胞的神经元放电模式的特征在于频率的单调累积， 差异作为时间的函数。然而，我们证明存储的信息并不 简单地在CA 1区域中恶化，但是用于时间的代码可以与用于通信系统的其它方面的可靠编码共存。 事件，例如空间位置或上下文。我们还发现CA 3包含一个非常精确的编码， 不随时间变化的背景和空间。新的初步数据显示，CA 2的效果与CA 3相反。Ca2 单元格表示经过的时间，但没有关于上下文的信息。基于这些发现，我们假设 在CA 1细胞群中，延长时间的神经元代码与空间和背景信息相结合， 引导人们记住前一事件的行为。使用行为测试和 在清醒行为的啮齿动物的单单位记录，这一假设是在三个目标测试：（1）确定是否 在海马CA 2神经网络中生成用于延长的时间间隔的神经元代码，（2）确定是否 来自海马CA 3亚区的输入对于维持海马CA 3亚区中稳定的记忆编码成分是必要的。 CA 1神经网络在小时和天，以及（3）确定是否在海马CA 1随时间变化的神经代码 而CA 2亚区与记忆“多久以前”相关。前两个目标是解决 子区域有助于神经代码的时变和稳定分量。除了定义函数 CA 2的时间编码和CA 3的功能，使稳定的记忆表示，我们还将问， 内嗅皮层可以在扩展的尺度上表示时间，因此是一个大脑区域， 在第三个目标中，我们将使用一个行为任务，在这个任务中，大鼠已经被证明， 记住“多久以前”在延长的时间段。我们将测量位置细胞中活动模式的相似性 两个时间点之间的群体，并确定神经元放电模式的变化是否对应于 老鼠对经过时间的估计总的来说，这些研究对于理解神经网络非常重要。 长期记忆稳定性和支持情景记忆的大脑结构中的时间事件编码机制 记忆理解记忆处理的关键机制将指导修复脑回路功能障碍的努力， 精神、神经和神经变性疾病。