Role of physiological patterns in hippocampal-prefrontal interactions

项目总结/摘要 海马体和内侧前额叶皮层（PFC）对学习和记忆引导行为都至关重要。 这些区域之间神经活动的协调对于记忆和认知过程是必要的， 然而，这些相互作用的性质及其作用仍不清楚。我们建立了多个时间表 这些区域的空间学习和记忆引导行为的神经表征， 在探索行为中的空间放电和θ振荡期间以及在尖波涟漪期间的协调 (SWR)在睡眠和清醒不动期的相关重放。在这里，我们将调查这些角色 生理网络模式的学习和记忆引导导航相结合的行为方法， 大鼠、高密度记录和因果操纵方法。(Aim 1）奖励对记忆的影响 表征是理解大脑前额叶活动模式在记忆引导的 行为特别是，已知奖励变化会影响海马体的重放，而重放被认为是 在将行动与奖励联系起来以进行强化学习方面发挥作用。为了直接回答这个问题，我们有 在TH-Cre大鼠中开发了用于多巴胺能腹侧被盖的光遗传学标记和鉴定的方法 区域（VTA）神经元编码奖励预测错误，同时记录海马 和前额叶合奏。我们将记录和操纵腹侧被盖区多巴胺神经元放电， 在学习新的空间规则过程中，大脑前额叶网络中的重放和任务表征。 (Aim 2）海马体和前额叶皮层都被认为是重要的上下文编码， 在不同背景下概括经验，但机制尚不清楚。我们的初步数据显示- 前额叶神经元的选择性编码在空间环境中保持不变，而海马CA 1 神经元在不同情境下重新映射。此外，我们还发现了协调的前额叶-前额叶波纹与 独立的皮层波动，具有不同的激活模式。我们将检查前额叶-前额叶 集合是规则表示和上下文编码的基础，θ序列是否保持编码 的当前上下文，并测试的假设，在协调涟漪重播，使关联跨越 contexts. (Aim 3）目标表示被认为是导航的核心，但目标编码的机制 和大脑前额叶-大脑前额叶在记忆引导导航中的表现仍不清楚。我们的初步数据 使用具有灵活目标位置和障碍的复杂2-D迷宫支持目标表示和重放， 海马和前额叶的集合。我们将测试海马和 在不动期间的前额叶重放事件支持即将到来的轨迹规划和目标表征 在轨迹执行期间用于在线维护的撞击θ序列。总的来说，我们的研究结果将提供新的 深入了解衰老和记忆障碍影响的基本学习和记忆机制 例如阿尔茨海默氏病。

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.