Role of physiological patterns in hippocampal-prefrontal interactions

生理模式在海马-前额叶相互作用中的作用

• 批准号: 10595305
• 负责人: Shantanu P Jadhav
• 金额: $ 40.42万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595305
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Automobile Driving; Behavior; Behavioral; Cells; Code; Complex; Data; Decision Making; Dementia; Disease; Dopamine; Dopaminergic Cell; Event; Exploratory Behavior; Functional disorder; Future; Goals; Hippocampus; Immobilization; Impaired cognition; Interruption; Learning; Link; Location; Maintenance; Maps; Medial; Mediating; Memory; Memory Disorders; Methods; Monitor; Nature; Neurons; Pattern; Physiological; Play; Prefrontal Cortex; Psychological reinforcement; Rattus; Retrieval; Rewards; Rodent; Role; Schizophrenia; Signal Transduction; Sleep; Testing; Ventral Tegmental Area; autism spectrum disorder; awake; cell assembly; cognitive ability; cognitive process; density; dopaminergic neuron; experience; flexibility; insight; memory consolidation; memory process; neural; neuromechanism; neurophysiology; neuropsychiatric disorder; novel; optogenetics

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.

项目概要/摘要 海马体和内侧前额叶皮层 (PFC) 对于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。我们制定了多个时间表 这些区域中用于空间学习和记忆引导行为的神经表征，以及区域间的神经表征 探索行为中的空间发射和 theta 振荡期间以及锐波波动期间的协调 (SWR) 与睡眠和清醒不动期间的重放相关。在这里，我们将研究这些角色的作用 通过结合行为方法来研究学习和记忆引导导航中的生理网络模式 大鼠、高密度录音和因果操纵方法。 （目标1）奖励对助记词的影响 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，奖励的变化会影响海马体的重放，而重放被认为会影响海马体的重放。 在将强化学习的行动与奖励联系起来方面发挥作用。为了直接解决这个问题，我们有 开发了 TH-Cre 大鼠的光遗传学标记和多巴胺能腹侧被盖识别方法 编码奖励预测误差的区域（VTA）神经元，与海马体的记录同时进行 和前额叶群。我们将记录和操纵 VTA 多巴胺神经元放电以检查其影响 在学习新空间规则期间海马前额叶网络的重放和任务表征。 （目标 2）众所周知，海马体和前额皮质对于上下文编码和 概括跨环境的经验，但机制尚不清楚。我们的初步数据显示规则- 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 CA1 神经元跨上下文重新映射。此外，我们还发现了协调的海马-前额波纹与 具有不同重新激活模式的独立皮质波纹。我们将检查海马-前额叶是否 集合是规则表示和上下文编码的基础，θ 序列是否维持编码 当前上下文，并测试协调涟漪期间重播能够实现跨区域关联的假设 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 用于记忆引导导航的海马前额叶表征仍不清楚。我们的初步数据 使用具有灵活目标位置和障碍的复杂二维迷宫支持目标表示和重放 导航期间的海马体和前额叶群。我们将检验海马和 不动期间的前额叶重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。总的来说，我们的结果将提供新颖的 深入了解受衰老和记忆障碍影响的基本学习和记忆机制 例如阿尔茨海默病。