Multiple mechanisms of neural coordination for associative memory processes

联想记忆过程的多种神经协调机制

• 批准号: 10616694
• 负责人: Shantanu P Jadhav
• 金额: $ 40.19万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10616694
• 关键词: Address; Animals; Automobile Driving; Behavior; Behavioral; Behavioral Paradigm; Brain; Brain region; Choice Behavior; Cognitive deficits; Communication; Cues; Decision Making; Detection; Disease; Electrodes; Feedback; Hippocampus; Impaired cognition; Learning; Link; Maintenance; Mediating; Memory; Methods; Monitor; Odors; Pattern; Performance; Periodicity; Phase; Physiological; Physiology; Population; Prefrontal Cortex; Rattus; Retrieval; Rewards; Role; Schizophrenia; Short-Term Memory; Site; Sleep; Stimulus; Symptoms; System; Techniques; Testing; Time; Work; autism spectrum disorder; behavior prediction; behavioral outcome; cognitive ability; cognitive function; common symptom; density; experimental study; gain of function; insight; loss of function; memory process; memory recall; neural; neuromechanism; neuropsychiatric disorder; novel; olfactory bulb; optogenetics; tool

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.

项目总结/摘要 已知涉及记忆的核心认知功能是由于大脑皮层活动的协调而出现的。 大脑中分布网络的神经群体水平。虽然神经协调是已知的， 虽然我们的研究涉及认知功能，但我们缺乏对介导这些功能的生理机制的完整理解。 协调和时间模式，以及这种协调是否可以在系统一级进行， 影响认知功能。我们的目标是通过解剖长期的生理机制来应对这一挑战- 范围协调在两个关键的大脑区域重要的记忆引导行为，海马和 前额皮质我们将使用一个联想记忆任务，利用气味的地方协会在一个空间 迷宫研究节律性网络振荡和时间模式的整体活动在 协调大脑前额叶网络我们已经发现，多个脑节律是突出的 这些区域在回忆，在线维护和联想记忆的形成过程中;我们将测试这些区域的功能。 一个新的假设，即相同的核心记忆网络动态地参与不同的节奏， 协调不同的记忆过程。此外，我们将直接使用 功能丧失和功能获得实验中的实时反馈方法。我们已经建立了相关的 通过将行为过程中的高密度记录与实时记录相结合， 使用电和光遗传学刺激检测网络模式和闭环反馈。一是 将使用多点记录，同时监测海马体和前额叶的整体活动， 皮层，以及在嗅球的活动，在大鼠，因为他们检索学习气味线索-地点协会， 引导奖励的行为选择。我们将研究不同的节奏，即β振荡（15-30 Hz）和θ振荡（6-10 Hz），介导这些网络在记忆回忆和 工作记忆的在线维护。我们将进一步确定振荡相位- 海马体和前额叶群的夹带活动是支持这些记忆的通信的基础 过程，并使用解码技术来研究时间协调的整体活动如何介导 联想记忆接下来，我们将使用实时测试来因果检验节奏模式在记忆中的作用。 用于光遗传学地操纵大脑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，如果扰动或增强活动在首选 用于通信的相位分别中断或增强记忆功能。最后，我们将使用这些 生理学和因果操纵方法，以测试在尖波波纹（150- 250赫兹）在形成新的协会和驾驶协调学习。因此，该提案将 提供了至关重要的洞察振荡网络活动的作用，在大脑前额叶协调， 联想记忆，并提供新的工具，通过操纵这种协调影响认知功能。