Temporally coordinated activity in the primate hippocampus supporting memory formation

项目摘要/摘要 海马体在新记忆的形成中起着关键作用；然而，它是如何形成的还不清楚 在记忆形成过程中，信息是由海马体网络组织和处理的。这个 海马体的微电路是高度相互连接的，这产生了健壮的、有时间结构的 横跨神经元集合的活动。微电路基元在其特征频率处发生共振 变得活跃起来，将海马神经元招募到可以在节律性中检测到的协调回路中 局部场势(LFP)。灵长类动物的海马LFP表现出一种复杂的振荡混合体 特征，并且在记忆任务期间，信号中通常没有主导频率。这是赤裸裸的 与啮齿动物在探索过程中选择性地出现显著的theta频段(6-10赫兹)振荡形成对比 和任务表现，因为动物积极地处理传入的信息。Theta-节律性活动 啮齿类动物的海马体通过内侧隔区的输入进行协调，内侧隔区是一条连接通路，是 在所有哺乳动物中都是保守的。尽管猴子缺乏这种持续的原型theta带活动，但在 LFP，跨物种解剖学的保存表明，存在着类似地支配着 灵长类动物的海马区信息处理。在这个提案中，我们将结合新的可用的 电生理学技术和创新的计算方法来量化和模拟复合波 灵长类LFP的信号。单机和LFP活动将从全范围同时记录 使用长期植入的超驱动器和线性电极阵列的海马体，而猴子则执行 虚拟现实中的空间记忆任务。此外，我们还将研究内侧隔刺激对 海马区振荡动力学和行为。我们将利用新的光谱分析技术 改进对以瞬变和不规则振荡为特征的LFP的解释。建议数 实验有以下潜在的结果：1)确定海马区振荡的关系 状态到神经元尖峰和记忆任务事件，2)开发数据驱动的计算模型， 描述在时间上和跨海马区展开的海马区振荡的模式 在记忆任务事件中，以及3)确定内侧隔驱动振荡活动的程度 调节海马体的主动处理。

Project Summary/Abstract The hippocampus plays a critical role in the formation of new memories; however, it is not clear how information is structured and processed by the hippocampal network in the service of memory formation. The microcircuitry of the hippocampus is richly interconnected, which produces robust, temporally-structured activity spanning ensembles of neurons. Microcircuit motifs resonate at characteristic frequencies when they become active, recruiting hippocampal neurons into coordinated circuits that can be detected in the rhythmicity of local field potentials (LFP). The hippocampal LFP in primates demonstrates a complex mixture of oscillatory signatures, and there is often no dominant frequency in the signal during memory tasks. This stands in stark contrast to the prominent theta band (6-10 Hz) oscillation that occurs in rodents selectively during exploration and task performance as the animal actively processes incoming information. Theta-rhythmic activity in the rodent hippocampus is coordinated by input from the medial septum, which is a connectional pathway that is conserved across all mammals. Although monkeys lack this sustained archetypal theta-band activity in the LFP, the preservation of anatomy across species suggests the presence of a circuit that would similarly govern hippocampal information processing in primates. In this proposal, we will combine newly available electrophysiological technology with innovative computational approaches to quantify and model complex signals of the primate LFP. Single-unit and LFP activity will be simultaneously recorded from the full extent of the hippocampus using chronically-implanted hyperdrives and linear electrode arrays while monkeys perform a spatial memory task in virtual reality. In addition, we will examine the effects of medial septum stimulation on hippocampal oscillatory dynamics and behavior. We will take advantage of novel spectral analysis techniques to improve interpretation of LFPs characterized by transient and irregular oscillations. The proposed experiments have the following potential outcomes: 1) to determine the relationship of hippocampal oscillatory states to neuronal spiking and memory task events, 2) to develop data-driven computational models that characterize patterns in hippocampal oscillations as they unfold in time and across hippocampal subfields during memory task events, and 3) to identify the extent to which the medial septum drives oscillatory activity mediating active processing in the hippocampus.