Role of physiological patterns in hippocampal-prefrontal interactions

项目摘要/摘要 海马体和前额叶皮质(PFC)对于学习和记忆引导行为都是至关重要的， 海马体是快速情景学习和记忆所必需的，而PFC在长时间学习和记忆中起着不可或缺的作用。 术语记忆、提取、工作记忆和决策。它们之间的神经活动的协调 这些区域是这些认知过程所必需的，然而，目前还不清楚神经活动的特征 与记忆相关的信息交流的中介互动，以及这些活动的明确角色 学习、检索和决策的模式。这项提案将调查突出的 结合大鼠行为方法的生理网络模式，高密度记录，以及一种新的 一种能够实时检测网络模式并中断网络间相互作用的闭环光遗传摄动技术 区域协调。首先，我们将同时和持续地监测神经群体的活动 海马体和PFC在学习过程中完成了一项新的空间记忆任务。先前的研究表明 两个显著的模式可以调节海马体-前额叶的相互作用； 与位置细胞活动相关的振荡，以及在 唤醒尖锐波纹(SWR)。我们将测试在初始探索支持期间是否重新激活唤醒SWR 通过建立海马-前额叶神经元之间的联系形成记忆 一致性在以后的利用过程中调解这些关联的检索，以支持持续决策 制作。接下来，我们将使用实时检测和闭环光遗传扰动来扰乱协调 在特定的生理模式中。我们将测试是否使用光遗传来干扰协调的重新激活 清醒时前额叶重新激活的扰动损害记忆形成和 行为学习。此外，我们将测试在theta一致性过程中是否干扰相位锁定的前额叶尖峰 损害提取和记忆引导的决策。最后，我们将调查在睡眠期间是否重新激活 而清醒的SWR在学习中扮演着不同的角色。我们将研究前额叶重新激活的差异 觉醒SWR与睡眠SWR，并通过干扰前额叶来测试睡眠SWR在巩固中的因果作用 在睡眠期间重新激活。总而言之，这些目标将提供对以下角色的综合、因果理解 在学习和记忆所必需的海马体-前额叶相互作用中显著的网络活动模式 引导性行为。因此，这项建议将为与这些疾病相关的记忆障碍提供至关重要的见解 如痴呆症、创伤后应激障碍、阿尔茨海默病，以及自闭症等神经精神障碍 和精神分裂症。

Project Summary/ Abstract The hippocampus and prefrontal cortex (PFC) are both critical for learning and memory-guided behavior, with the hippocampus necessary for rapid episodic learning and memory, and PFC playing an integral role in long- term memory, retrieval, working memory and decision making. Coordination of neural activity between these regions is necessary for these cognitive processes, however, it is still unclear what features of neural activity mediate interactions for communication of memory-related information, and the explicit roles of these activity patterns in learning, retrieval and decision making. This proposal will investigate the roles of prominent physiological network patterns by combining behavioral methods in rats, high-density recording, and a novel closed-loop optogenetic perturbation technique that can detect network patterns in real-time and disrupt inter- regional coordination. First, we will simultaneously and continuously monitor activity of neural populations in the hippocampus and PFC over the course of learning of a novel spatial memory task. Previous work suggests that two prominent patterns can mediate hippocampal-prefrontal interactions; coherence during theta oscillations associated with place cell activity, and coordinated reactivation of behavioral experiences during awake sharp-wave ripples (SWRs). We will test if awake SWR reactivation during initial exploration supports memory formation by establishing associations between hippocampal-prefrontal neurons, and if theta coherence mediates retrieval of these associations during later exploitation to support ongoing decision making. Next we will use real-time detection and closed-loop optogenetic perturbation to disrupt coordination during specific physiological patterns. We will test if disrupting coordinated reactivation using optogenetic perturbation of prefrontal reactivation during awake hippocampal SWRs impairs memory formation and behavioral learning. Further, we will test if disrupting phase-locked prefrontal spiking during theta coherence impairs retrieval and memory-guided decision making. Finally, we will investigate if reactivation during sleep and awake SWRs play different roles in learning. We will examine differences in prefrontal reactivation for awake vs. sleep SWRs, and test the causal role of sleep SWRs in consolidation by disrupting prefrontal reactivation during sleep. Together, these aims will provide an integrated, causal understanding of the role of prominent network activity patterns in hippocampal-prefrontal interactions necessary for learning and memory- guided behavior. This proposal will thus provide crucial insight into memory disorders associated with these regions such as dementia, PTSD, Alzhiemer's disease, and also neuropsychiatric disorders such as autism and schizophrenia.