Role of physiological patterns in hippocampal-prefrontal interactions

项目摘要/摘要 海马体和内侧前额叶皮质(PFC)对学习和记忆引导行为都是至关重要的。 这些区域之间的神经活动协调对于记忆和认知过程是必要的， 然而，这些互动的性质和它们的作用仍然不清楚。我们已经建立了多个时间尺度 这些区域的空间学习和记忆引导行为的神经表征，以及区域间的 在探索行为中的空间激发和theta振荡以及尖锐波纹中的协调 (SWR)睡眠和清醒不动期间的相关重播。在这里，我们将调查这些角色 学习记忆引导导航中的生理网络模式 大鼠、高密度记录和因果操作方法。(目标1)奖励对记忆力的影响 表征是理解海马-前额叶活动模式在记忆引导中的作用的关键 行为。特别是，众所周知，奖赏的变化会影响海马区的重演，而重演被认为是 发挥作用，将强化学习的行动与奖励联系起来。为了直接解决这个问题，我们有 TH-CRE大鼠视遗传标记和多巴胺能腹侧被盖识别方法的建立 编码奖赏预测误差的区域(VTA)神经元，与来自海马区的记录同步 以及前额叶合奏。我们将记录和操纵VTA多巴胺神经元的放电，以检查其影响 新空间规则学习过程中海马-前额叶网络中的重演和任务表征。 (目标2)已知的是，海马体和前额叶皮质对语境编码和 在不同背景下总结经验，但机制尚不清楚。我们的初步数据显示规则是- 前额叶神经元跨空间环境维持的选择性编码，而海马区CA1 神经元在不同的环境中重新映射。此外，我们还发现协调的海马额前波纹VS 独立的皮质波纹和不同的重新激活模式。我们将检查海马体前额叶 无论theta序列是否保持编码，集合都是规则表示和上下文编码的基础 并测试这样的假设：在协调的涟漪期间重放能够使关联跨越 上下文。(目标3)目标表示被认为是导航的核心，但目标编码的机制 记忆引导导航的海马体前额叶表征仍不清楚。我们的初步数据 使用具有灵活的目标位置和障碍的复杂的2-d迷宫支持目标表示和回放 导航过程中的海马区和前额区。我们将检验假设，即海马体和 不动期间的前额回放事件支持对即将到来的轨迹和目标表示的规划 影响轨迹执行期间在线维护的theta序列。总体而言，我们的结果将提供新颖的 深入了解影响衰老和记忆障碍的基本学习和记忆机制 比如阿尔茨海默氏症。

Project Summary/ Abstract The hippocampus and medial prefrontal cortex (PFC) are both critical for learning and memory-guided behavior. Coordination of neural activity between these regions is necessary for memory and cognitive processes, however, the nature of these interactions and their roles are still unclear. We have established multiple timescale neural representations in these regions for spatial learning and memory-guided behavior, with inter-regional coordination during spatial firing and theta oscillations in exploratory behavior, and during sharp-wave ripple (SWR) associated replay in sleep and awake immobility periods. Here, we will investigate the roles of these physiological network patterns in learning and memory-guided navigation by combining behavioral methods in rats, high-density recordings, and causal manipulation methods. (Aim 1) The influence of reward on mnemonic representations is key to understanding the role of hippocampal-prefrontal activity patterns in memory-guided behavior. In particular, it is known that reward changes influence hippocampal replay, and replay is thought to play a role in linking actions to reward for reinforcement learning. To address this question directly, we have developed methods in TH-Cre rats for optogenetic tagging and identification of dopaminergic ventral tegmental area (VTA) neurons which encode reward prediction error, simultaneously with recordings from hippocampal and prefrontal ensembles. We will record and manipulate VTA dopamine neuron firing to examine the influence on replay and task representations in the hippocampal-prefrontal network during learning of new spatial rules. (Aim 2) The hippocampus and prefrontal cortex are both known to be important for contextual encoding and generalizing experiences across contexts, but the mechanisms are unclear. Our preliminary data show rule- selective encoding by prefrontal neurons that is maintained across spatial contexts, whereas hippocampal CA1 neurons remap across contexts. Further, we have also found coordinated hippocampal-prefrontal ripples vs independent cortical ripples with distinct reactivation patterns. We will examine whether hippocampal-prefrontal ensembles underlie rule representations and contextual encoding, whether theta sequences maintain encoding of current context, and test the hypothesis that replay during coordinated ripples enables associations across contexts. (Aim 3) Goal representations are considered central to navigation, but the mechanisms for goal coding and hippocampal-prefrontal representations for memory-guided navigation are still unclear. Our preliminary data using a complex 2-d maze with flexible goal locations and barriers supports goal representations and replay by hippocampal and prefrontal ensembles during navigation. We will test the hypotheses that hippocampal and prefrontal replay events during immobility support planning of upcoming trajectories, and goal representations impact theta sequences for online maintenance during trajectory execution. Overall, our results will provide novel insight into fundamental learning and memory mechanisms that are affected in aging and memory disorders such as Alzheimer’s disease.