Multiple mechanisms of neural coordination for associative memory processes

项目摘要/摘要 已知，涉及记忆的核心认知功能是大脑活动协调的结果 大脑中分布的网络中的神经种群的水平。尽管已知神经协调 参与认知功能，我们对调节的生理机制缺乏完整的了解 协调和时间模式，以及这种协调是否可以在系统一级有针对性地 影响认知功能。我们的目标是通过剖析长时间的生理机制来应对这一挑战。 对记忆引导行为非常重要的两个关键脑区--海马体和 前额叶皮质。我们将使用一项联想记忆任务，它利用空间中的气味-地点关联 迷宫以研究节律性网络振荡和时间模式的集合活动在脑内的作用 协调海马体-前额叶网络。我们已经发现，多重大脑节律在 这些区域在回忆、在线维护和形成联想记忆的过程中；我们将测试 新的假设，即相同的核心内存网络被不同的节奏动态地参与 在不同的记忆过程中的协调。此外，我们将使用以下命令直接操作此协调 功能损失和功能增益实验中的实时反馈方法。我们已经建立了相关的 通过将行为期间的高密度记录与实时记录相结合来实施此方法的专业知识 使用电刺激和光遗传刺激检测网络模式和闭环反馈。首先，我们 将使用多点记录来同时监测海马体和前额叶的整体活动 在大鼠提取习得的气味线索-位置联系时，大脑皮层以及嗅球中的活动 引导行为选择以换取奖励。我们将研究不同的节律，即β振荡(15-30 Hz)和theta振荡(6-10 hz)，调节这些网络在记忆回忆和 分别在工作记忆期间进行在线维护。我们将进一步确定振荡相位如何- 海马区和前额叶区的集中活动是支持这些记忆的沟通的基础 过程，并使用解码技术来研究时间协调的集合活动如何调节 联想记忆。接下来，我们将使用实时测试来因果测试节奏模式在记忆中的作用 光遗传操作海马-前额叶协调的检测和闭环反馈 普遍振荡的特定阶段。特别是，我们将测试是否干扰或增强首选的活动 交流的阶段分别中断或增强记忆功能。最后，我们将使用这些 生理学和因果操作方法，以测试在尖锐波纹(150- 250赫兹)在学习过程中形成新的联想和驱动协调。因此，这项提议将 对振荡网络活动在海马-前额叶协调中的作用提供重要的见解 联想记忆，并为通过操纵这种协调来影响认知功能提供了新的工具。

Project Summary/ Abstract Core cognitive functions involving memory are known to emerge as a result of coordination of activity at the level of neural populations across distributed networks in the brain. Although neural coordination is known to be involved in cognitive function, we lack a complete understanding of physiological mechanisms that mediate coordination and temporal patterns, and whether this coordination can be targeted at the systems-level to impact cognitive function. We aim to address this challenge by dissecting physiological mechanisms of long- range coordination in two key brain regions important for memory-guided behavior, the hippocampus and prefrontal cortex. We will use an associative memory task that utilizes odor-place associations in a spatial maze to investigate the role of rhythmic network oscillations and temporally patterned ensemble activity in coordinating the hippocampal-prefrontal network. We have found that multiple brain rhythms are prominent in these regions during recall, online maintenance, and formation of associative memories; and we will test the novel hypothesis that the same core memory networks are dynamically engaged by distinct rhythms for coordination during different memory processes. Further, we will directly manipulate this coordination using real-time feedback methods in loss- and gain-of-function experiments. We have established the relevant expertise to carry out this approach by combining high-density recordings during behavior with real-time detection of network patterns and closed-loop feedback using electrical and optogenetic stimulation. First, we will use multisite recording to simultaneously monitor ensemble activity in the hippocampus and prefrontal cortex, as well as activity in the olfactory bulb, in rats as they retrieve learned odor cue-place associations to guide behavioral choices for reward. We will investigate how distinct rhythms, namely beta oscillations (15-30 Hz) and theta oscillations (6-10 Hz), mediate coordination of these networks during memory recall and for online maintenance during working memory respectively. We will further determine how oscillation phase- entrained activity of hippocampal and prefrontal populations underlies communication to support these memory processes, and use decoding techniques to investigate how temporally coordinated ensemble activity mediates associative memories. Next, we will causally test the role of rhythmic patterns in memory using real-time detection and closed-loop feedback for optogenetically manipulating hippocampal-prefrontal coordination at specific phases of prevalent oscillations. In particular, we will test if perturbing or enhancing activity at preferred phases for communication disrupts or enhances memory function respectively. Finally, we will use these physiology and causal manipulation approaches to test the role of reactivation during sharp-wave ripples (150- 250 Hz) in formation of novel associations and driving coordination during learning. This proposal will thus provide crucial insight in the role of oscillatory network activity in hippocampal-prefrontal coordination for associative memory, and provide novel tools for impacting cognitive function by manipulating this coordination.